Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
The protein tau is implicated in several brain disorders, including Alzheimer's disease, suggesting that it could be a target of therapeutics. However, because it is unclear how the pleiotropic roles of tau lead to neural pathology in different brain diseases, drug development remains challengi...
Saved in:
| Published in | Science (American Association for the Advancement of Science) Vol. 371; no. 6532 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
The American Association for the Advancement of Science
26.02.2021
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | The protein tau is implicated in several brain disorders, including Alzheimer's disease, suggesting that it could be a target of therapeutics. However, because it is unclear how the pleiotropic roles of tau lead to neural pathology in different brain diseases, drug development remains challenging. Chang
et al.
review the possible mechanisms of tau in brain diseases and possible paths forward to improving research and drug development.
Science
, this issue p.
eabb8255
Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer’s disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions. |
|---|---|
| AbstractList | Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer's disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions. The protein tau is implicated in several brain disorders, including Alzheimer's disease, suggesting that it could be a target of therapeutics. However, because it is unclear how the pleiotropic roles of tau lead to neural pathology in different brain diseases, drug development remains challenging. Chang et al. review the possible mechanisms of tau in brain diseases and possible paths forward to improving research and drug development. Science , this issue p. eabb8255 Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer’s disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions. Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer's disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions.Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer's disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions. Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer’s disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions. Summary Figure: Potential tau pathomechanisms. Developing effective tau-targeting therapeutics will require a better understanding of how exactly tau contributes to Alzheimer’s disease and other disorders of the central nervous system. Potential mechanisms likely fall into the three broad categories shown. However, the relative pathogenic impact and overall importance of individual mechanisms have yet to be defined in truly disease-relevant contexts and may differ among diseases and even patients. The blue box on the right indicates tau activities that do not directly mediate but indirectly promote or facilitate pathogenic processes. Expanding efforts to develop tau-targeting therapeutics will shed light on this enigmatic protein and could yield better treatments for multiple brain disorders. The many faces of tauThe protein tau is implicated in several brain disorders, including Alzheimer's disease, suggesting that it could be a target of therapeutics. However, because it is unclear how the pleiotropic roles of tau lead to neural pathology in different brain diseases, drug development remains challenging. Chang et al. review the possible mechanisms of tau in brain diseases and possible paths forward to improving research and drug development.Science, this issue p. eabb8255BACKGROUNDThe microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer’s disease and a range of other neurodegenerative disorders (called “tauopathies”). As the number of people with tauopathies is rising in aging populations across the world, interest in the fundamental biology of this protein and in the development of tau-targeting treatments has been expanding rapidly. Recent insights into the complexity of this intrinsically disordered protein suggest that tau is a worthy but challenging target whose multifaceted nature will likely require a multipronged therapeutic approach. Derived from a single gene by alternative splicing, six major isoforms of tau have been identified in the human brain. In addition, tau is subject to many different posttranslational modifications, further indicating that it may be regulated by multiple processes and may participate in diverse functions.ADVANCESTau is widely presumed to stabilize microtubules. However, the experimental reduction or ablation of tau in vivo does not alter many neural properties and processes that likely depend on microtubules, including neuronal integrity, axonal transport, synapse formation, and complex brain functions. Although tau reduction seems to have minimal effects on otherwise unmanipulated brains, it can prevent or diminish aberrant cell signaling, neural network dysfunctions (e.g., epileptic activity), and behavioral alterations caused by diverse disease processes, which suggests that tau activities are needed for other pathogenic triggers to cause these derangements. In addition to this “enabling bystander” role, tau’s interactions with a large number of other proteins can cause adverse gains of function, which are associated with—and possibly caused by—the formation of abnormal tau structures and assemblies. Because abnormal forms of tau trigger a plethora of pathomechanisms, targeting individual downstream mechanisms may have limited therapeutic impact, unless the relative pathogenic importance of the specific mechanism has been well established in experimental models that allow for conclusive validation of cause-and-effect relationships. Although much attention has focused on the abnormal aggregation of tau in tauopathies and on the ability of tau “seeds” to spread from neuron to neuron, internalization of propagating tau does not appear to impair neuronal survival or brain functions. Moreover, tau reduction prevents or diminishes neural network dysfunction and behavioral abnormalities also in disease models that do not have abnormal tau inclusions, which suggests that there is more to tau than aggregation and propagation. A promising diversification of tau-targeting therapeutic strategies is beginning to address this complexity. Lowering overall tau levels may have the greatest potential, as this strategy bypasses the unresolved questions of which forms of tau and which downstream mechanisms are most detrimental in any given condition.OUTLOOKMany efforts to develop better treatments for neurodegenerative diseases have failed, in large part because of an inadequate understanding of disease mechanisms and, perhaps, because too many fundamental knowledge gaps, alternative interpretations of data, and methodological complexities did not receive the attention they deserved. This Review highlights important gaps in the understanding of tau and the methodological advances needed to fill them. It also pinpoints obstacles that could complicate the translation of tau-related scientific discoveries into better therapeutics and offers pragmatic strategies to overcome these challenges. Despite the extraordinary progress that has been made to date, the main physiological functions that tau fulfills in the adult and aging brain remain to be defined. Another critical objective is to develop better experimental models and technologies to rigorously compare different tau species and pathomechanisms, particularly their relative impacts on neuronal functions and survival in vivo. For the development of truly informative biomarkers and effective therapeutics, it will be critical to rigorously differentiate between associations and cause-and-effect relationships. Until the main drivers of neuronal dysfunction and demise have been identified for Alzheimer’s disease and other conditions in which tau has a causal or enabling role, it seems prudent to focus on pragmatic strategies, such as overall tau reduction, while also expanding efforts to further validate the importance of more-specific targets and approaches. Investigational approaches to lower overall tau levels include tau-targeting antisense oligonucleotides, which have advanced into a clinical trial for early Alzheimer’s disease, and the development of small-molecule drugs that can modulate the production or degradation of tau. The most desirable tau-targeting therapeutics would be efficacious across diverse tauopathies, as well as affordable, easy to access, and well tolerated when administered over long periods of time to fragile groups of people who likely take multiple other medications.Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer’s disease, other neurodegenerative conditions, autism, and epilepsy. Tau is abundant in neurons and interacts with microtubules, but its main functions in the brain remain to be defined. These functions may involve the regulation of signaling pathways relevant to diverse biological processes. Informative disease models have revealed a plethora of abnormal tau species and mechanisms that might contribute to neuronal dysfunction and loss, but the relative importance of their respective contributions is uncertain. This knowledge gap poses major obstacles to the development of truly impactful therapeutic strategies. The current expansion and intensification of efforts to translate mechanistic insights into tau-related therapeutics should address this issue and could deliver better treatments for a host of devastating conditions. |
| Author | Shao, Eric Mucke, Lennart Chang, Che-Wei |
| AuthorAffiliation | 2 Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA 1 Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA |
| AuthorAffiliation_xml | – name: 1 Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA – name: 2 Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA |
| Author_xml | – sequence: 1 givenname: Che-Wei orcidid: 0000-0003-1043-581X surname: Chang fullname: Chang, Che-Wei organization: Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA – sequence: 2 givenname: Eric orcidid: 0000-0001-5307-8264 surname: Shao fullname: Shao, Eric organization: Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA – sequence: 3 givenname: Lennart orcidid: 0000-0001-6256-9559 surname: Mucke fullname: Mucke, Lennart organization: Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA., Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33632820$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1kc1rVDEUxYNU7LS6dicP3LiZNp9v8lwIpVQrFNzUpYSb5L5pyptkTPIG-t-boVOxBVch9_7O4STnhBzFFJGQ94yeMcb78-ICRodnYK3mSr0iC0YHtRw4FUdkQanol5qu1DE5KeWe0rYbxBtyLEQvuOZ0QX7dwvy5u4pgJ8xdGjsfdpgLdjZDiO1WUvZt0EH0XYW8xrqnMmyDnx463KVpF-K6q3fYZjjX4LpSM1RcByxvyesRpoLvDucp-fn16vbyennz49v3y4ubpZN6VZccuOcA1vNeinEYYWWBj1R5aQfhrRdSKk0dl3xUljHRI_dWeuFAaM2ZEqfky6PvdrYb9A5jizCZbQ4byA8mQTDPNzHcmXXaGc2Y7hVtBp8OBjn9nrFUswnF4TRBxDQXw-Ug-SDZSjT04wv0Ps05tuftKaF6qSlr1Id_E_2N8vTzDVCPgMuplIyjcaFCDWkfMEyGUbNv2BwaNoeGm-78he7J-n-KPx-lrXQ |
| CitedBy_id | crossref_primary_10_1016_j_nbd_2022_105632 crossref_primary_10_3390_biology10101047 crossref_primary_10_1002_ijch_202300104 crossref_primary_10_1021_acsnano_4c14571 crossref_primary_10_3389_fnins_2024_1345225 crossref_primary_10_1523_ENEURO_0089_21_2021 crossref_primary_10_3389_fnins_2023_1145318 crossref_primary_10_3934_mbe_2023741 crossref_primary_10_1002_alz_13028 crossref_primary_10_1038_s41467_024_45851_6 crossref_primary_10_15212_AMM_2024_0075 crossref_primary_10_3390_ijms22147475 crossref_primary_10_1212_WNL_0000000000207663 crossref_primary_10_1172_JCI168549 crossref_primary_10_1002_adhm_202400149 crossref_primary_10_1021_acschembio_2c00919 crossref_primary_10_1039_D4SC07379G crossref_primary_10_1111_bpa_13317 crossref_primary_10_1080_14728222_2023_2206561 crossref_primary_10_2174_1570159X23666241101093436 crossref_primary_10_3233_JAD_220351 crossref_primary_10_1039_D4SC05469E crossref_primary_10_15252_embj_2022112101 crossref_primary_10_1111_epi_17355 crossref_primary_10_3389_fnagi_2021_761913 crossref_primary_10_1016_j_lanhl_2024_100678 crossref_primary_10_1073_pnas_2206240119 crossref_primary_10_1039_D1CS00127B crossref_primary_10_2147_NDT_S393773 crossref_primary_10_1038_s41467_022_32951_4 crossref_primary_10_1002_bmm2_12011 crossref_primary_10_1186_s12979_024_00437_0 crossref_primary_10_3390_biomedicines11123156 crossref_primary_10_1016_j_celrep_2021_110141 crossref_primary_10_1016_j_chembiol_2024_09_003 crossref_primary_10_1126_scitranslmed_abm5527 crossref_primary_10_15252_embj_2021110242 crossref_primary_10_1038_s41467_023_42295_2 crossref_primary_10_15252_embj_2022111265 crossref_primary_10_1038_s41583_024_00797_y crossref_primary_10_3390_biomedicines9121910 crossref_primary_10_3390_cells11111735 crossref_primary_10_1016_j_isci_2021_103658 crossref_primary_10_3390_pharmaceutics16111443 crossref_primary_10_1523_JNEUROSCI_1225_24_2024 crossref_primary_10_1016_j_molimm_2022_02_006 crossref_primary_10_1186_s13024_022_00521_3 crossref_primary_10_1007_s12031_023_02143_w crossref_primary_10_1177_13872877251320123 crossref_primary_10_3390_neuroglia6010001 crossref_primary_10_1007_s11010_024_05164_0 crossref_primary_10_3389_fphar_2024_1459655 crossref_primary_10_1523_ENEURO_0052_23_2023 crossref_primary_10_1016_j_ecoenv_2022_114151 crossref_primary_10_1016_j_snb_2024_136797 crossref_primary_10_1126_sciadv_abl8809 crossref_primary_10_1016_j_ajhg_2023_12_015 crossref_primary_10_1016_j_neuron_2021_07_013 crossref_primary_10_1093_hmg_ddad049 crossref_primary_10_14283_jpad_2023_106 crossref_primary_10_1016_j_bbamcr_2021_119116 crossref_primary_10_1186_s40478_024_01920_x crossref_primary_10_3390_molecules26175113 crossref_primary_10_3390_biom12121792 crossref_primary_10_1016_j_ejmech_2023_116065 crossref_primary_10_1002_alz_13533 crossref_primary_10_1016_j_isci_2021_103245 crossref_primary_10_1016_j_neuroscience_2022_11_003 crossref_primary_10_1016_j_celrep_2022_111249 crossref_primary_10_1016_j_xgen_2024_100563 crossref_primary_10_1093_braincomms_fcae333 crossref_primary_10_1021_acsnano_4c16435 crossref_primary_10_1038_s41398_025_03304_8 crossref_primary_10_1001_jamaneurol_2021_5181 crossref_primary_10_1126_sciadv_adm8449 crossref_primary_10_1177_15357597221126332 crossref_primary_10_1186_s12877_022_03454_0 crossref_primary_10_3233_JAD_230927 crossref_primary_10_1016_j_jconrel_2024_01_019 crossref_primary_10_1016_j_freeradbiomed_2022_01_025 crossref_primary_10_1111_cns_70305 crossref_primary_10_1186_s13073_023_01205_3 crossref_primary_10_1186_s13075_023_03133_4 crossref_primary_10_1016_j_celrep_2021_109855 crossref_primary_10_1016_j_cell_2023_09_023 crossref_primary_10_1111_gtc_13101 crossref_primary_10_3390_biomedicines10081890 crossref_primary_10_1016_j_brainres_2024_148823 crossref_primary_10_1016_j_cell_2022_09_029 crossref_primary_10_3389_fnagi_2021_751897 crossref_primary_10_3390_ijms22094805 crossref_primary_10_3390_biomedicines10081772 crossref_primary_10_1016_j_omtn_2022_07_027 crossref_primary_10_1186_s13195_023_01321_7 crossref_primary_10_3390_biomedicines10092261 crossref_primary_10_1111_jnc_15909 crossref_primary_10_1002_anie_202423801 crossref_primary_10_3389_fnmol_2022_1019999 crossref_primary_10_1016_j_nbd_2024_106656 crossref_primary_10_1007_s10735_025_10361_2 crossref_primary_10_1001_jamaneurol_2022_1375 crossref_primary_10_1038_s41422_024_01016_0 crossref_primary_10_1038_s41573_021_00371_6 crossref_primary_10_1146_annurev_pathmechdis_030421_112756 crossref_primary_10_12677_acm_2024_1482177 crossref_primary_10_1016_j_cell_2021_12_041 crossref_primary_10_1016_j_biomaterials_2024_123042 crossref_primary_10_1186_s40478_024_01839_3 crossref_primary_10_3389_fnins_2022_1021131 crossref_primary_10_3389_fimmu_2022_782434 crossref_primary_10_1002_ange_202423801 crossref_primary_10_1016_j_smim_2022_101628 crossref_primary_10_1007_s12192_023_01363_8 crossref_primary_10_3390_ijms23020851 crossref_primary_10_1016_j_biosx_2024_100528 crossref_primary_10_1016_j_neuroscience_2022_01_005 crossref_primary_10_1016_j_expneurol_2023_114355 crossref_primary_10_1002_alz_14250 crossref_primary_10_1016_j_celrep_2023_113252 crossref_primary_10_1007_s11357_022_00526_2 crossref_primary_10_1176_appi_neuropsych_21060166 crossref_primary_10_2139_ssrn_4114949 crossref_primary_10_1002_cm_21790 crossref_primary_10_1016_j_neubiorev_2022_104541 crossref_primary_10_1007_s12035_023_03720_1 crossref_primary_10_1016_j_neuroscience_2022_10_014 crossref_primary_10_1038_s41380_023_02113_z crossref_primary_10_1021_acs_jpcb_1c10752 crossref_primary_10_1007_s00018_021_03986_5 crossref_primary_10_12677_ACM_2023_1361387 crossref_primary_10_1038_s43587_021_00076_w crossref_primary_10_1021_acschemneuro_1c00554 crossref_primary_10_1172_JCI169064 crossref_primary_10_1111_jnc_16053 crossref_primary_10_1016_S1474_4422_22_00168_5 crossref_primary_10_1093_brain_awab433 crossref_primary_10_1016_j_celrep_2023_112152 crossref_primary_10_1016_j_ymthe_2024_01_033 crossref_primary_10_3390_cells10040721 crossref_primary_10_1080_1028415X_2022_2145426 crossref_primary_10_1093_braincomms_fcae017 crossref_primary_10_1016_S1474_4422_23_00108_4 crossref_primary_10_1093_braincomms_fcac235 crossref_primary_10_3390_ijms241813900 |
| Cites_doi | 10.1126/science.1194653 10.1038/nature24016 10.1001/jama.2020.12134 10.3389/fneur.2013.00114 10.1385/JMN:17:2:225 10.1016/j.cub.2018.05.045 10.1126/science.1062097 10.1038/s41591-018-0004-z 10.1056/NEJMoa1900907 10.1002/hipo.20798 10.1038/s41593-018-0298-7 10.1016/S0002-9440(10)64963-2 10.1186/s40478-017-0489-6 10.1083/jcb.201407065 10.1016/j.neurobiolaging.2014.05.001 10.1126/science.aah6205 10.1038/s41467-017-00618-0 10.1038/ng.2257 10.1523/JNEUROSCI.2369-17.2018 10.1074/jbc.M115.641902 10.1186/s13024-015-0025-8 10.1126/science.1058189 10.1001/jamaneurol.2020.0989 10.1016/j.neurobiolaging.2014.09.007 10.1038/s41593-017-0022-z 10.1074/jbc.RA119.007527 10.7554/eLife.45457 10.1186/s40478-015-0210-6 10.1038/s41586-019-1769-z 10.1523/JNEUROSCI.2107-13.2013 10.1016/j.neuron.2017.04.010 10.1038/s41591-020-0938-9 10.1038/embor.2013.15 10.1126/scitranslmed.aag0481 10.1093/brain/awv222 10.1101/gr.233866.117 10.1186/s13100-019-0176-1 10.1001/archneur.63.9.1312 10.1016/j.neuron.2018.10.031 10.1083/jcb.150.5.989 10.3389/fnins.2019.00659 10.1038/srep19393 10.1126/science.1141736 10.1523/JNEUROSCI.0188-12.2012 10.2174/15672050113109990143 10.1126/scitranslmed.aat3005 10.3389/fnins.2012.00104 10.1093/brain/awx005 10.1038/ncb1901 10.1016/j.neurobiolaging.2011.10.020 10.1523/JNEUROSCI.4361-12.2013 10.1084/jem.20190980 10.1093/brain/awy117 10.1091/mbc.e14-06-1099 10.1523/JNEUROSCI.23-18-06972.2003 10.1186/s40478-019-0664-z 10.1073/pnas.91.12.5562 10.1016/j.neuron.2018.02.015 10.1016/j.cell.2019.11.031 10.1172/JCI137040 10.1021/bi00035a017 10.1186/1750-1326-9-43 10.1016/j.neurobiolaging.2014.05.005 10.1038/s41582-018-0013-z 10.1038/s41588-018-0311-9 10.1093/brain/aww187 10.1073/pnas.092136199 10.1038/nrn2055 10.1007/978-981-32-9358-8_28 10.1038/s41588-019-0358-2 10.1016/j.celrep.2018.07.072 10.1038/nrn.2015.1 10.1098/rstb.2013.0144 10.1126/scitranslmed.aau5732 10.1038/nn.4067 10.1007/s00401-014-1254-6 10.3233/JAD-2010-100285 10.1016/j.smrv.2014.03.007 10.1186/s13024-017-0231-7 10.1371/journal.pone.0084849 10.1523/JNEUROSCI.1590-19.2019 10.1186/s13024-019-0354-0 10.1038/nm.4199 10.1016/S2352-3018(20)30069-2 10.1016/j.nbd.2019.01.008 10.1016/j.cell.2012.02.046 10.1016/j.sbi.2020.05.011 10.1523/JNEUROSCI.4922-11.2012 10.1016/j.neuron.2016.03.005 10.1038/s41467-019-10428-1 10.1007/978-981-32-9358-8_1 10.1016/j.neurobiolaging.2012.12.003 10.1038/nature20587 10.1038/s41582-020-0348-0 10.1016/j.neuron.2018.01.022 10.1016/j.neuron.2016.09.055 10.1083/jcb.103.6.2739 10.1523/JNEUROSCI.4040-10.2010 10.1016/j.neuron.2009.05.012 10.1126/science.1113694 10.1186/s13024-019-0306-8 10.1523/JNEUROSCI.5242-07.2008 10.15252/embr.201541438 10.1016/j.stem.2018.12.013 10.1084/jem.20161731 10.1038/s41586-019-1688-z 10.1038/s41586-020-2156-5 10.1186/s40478-019-0723-5 10.1016/j.cell.2012.02.040 10.1016/j.stemcr.2017.06.005 10.1038/369488a0 10.1038/s41591-020-0781-z 10.1186/s40478-019-0754-y 10.1016/j.neuron.2010.08.044 10.1001/jamaneurol.2018.2505 10.1038/nn.4328 10.1091/mbc.6.12.1887 10.1016/j.neuron.2018.06.003 10.1016/j.neuron.2020.01.038 10.1523/JNEUROSCI.4315-03.2004 10.1016/j.neuron.2019.08.008 10.1016/j.ajpath.2013.11.021 10.1523/JNEUROSCI.4152-10.2011 10.1523/JNEUROSCI.2552-14.2015 10.1056/NEJMoa1710504 10.1016/j.nbd.2018.05.020 10.1021/jacs.0c00768 10.1111/acel.12692 10.31887/DCNS.2012.14.4/gbuzsaki 10.1002/ana.24230 10.1016/j.nbd.2013.06.005 10.1126/science.aav2546 10.1038/s41593-018-0194-1 10.1016/j.neulet.2020.134919 10.1016/j.cell.2010.06.036 10.1021/acs.analchem.5b04509 10.1038/nm.2613 10.1016/j.conb.2018.04.027 10.1038/nm.4011 10.1074/jbc.M117.784702 10.1523/JNEUROSCI.3439-13.2014 10.1016/j.neurobiolaging.2017.05.017 10.1523/JNEUROSCI.2642-12.2013 10.1084/jem.20131685 10.1093/hmg/ddr603 10.1016/j.celrep.2018.05.004 10.1093/hmg/dds161 10.1038/s41580-019-0101-y 10.1007/s00401-017-1674-1 |
| ContentType | Journal Article |
| Copyright | Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
| Copyright_xml | – notice: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. – notice: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QF 7QG 7QL 7QP 7QQ 7QR 7SC 7SE 7SN 7SP 7SR 7SS 7T7 7TA 7TB 7TK 7TM 7U5 7U9 8BQ 8FD C1K F28 FR3 H8D H8G H94 JG9 JQ2 K9. KR7 L7M L~C L~D M7N P64 RC3 7X8 5PM |
| DOI | 10.1126/science.abb8255 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Aluminium Industry Abstracts Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Ceramic Abstracts Chemoreception Abstracts Computer and Information Systems Abstracts Corrosion Abstracts Ecology Abstracts Electronics & Communications Abstracts Engineered Materials Abstracts Entomology Abstracts (Full archive) Industrial and Applied Microbiology Abstracts (Microbiology A) Materials Business File Mechanical & Transportation Engineering Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Solid State and Superconductivity Abstracts Virology and AIDS Abstracts METADEX Technology Research Database Environmental Sciences and Pollution Management ANTE: Abstracts in New Technology & Engineering Engineering Research Database Aerospace Database Copper Technical Reference Library AIDS and Cancer Research Abstracts Materials Research Database ProQuest Computer Science Collection ProQuest Health & Medical Complete (Alumni) Civil Engineering Abstracts Advanced Technologies Database with Aerospace Computer and Information Systems Abstracts Academic Computer and Information Systems Abstracts Professional Algology Mycology and Protozoology Abstracts (Microbiology C) Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Materials Research Database Technology Research Database Computer and Information Systems Abstracts – Academic Mechanical & Transportation Engineering Abstracts Nucleic Acids Abstracts ProQuest Computer Science Collection Computer and Information Systems Abstracts ProQuest Health & Medical Complete (Alumni) Materials Business File Environmental Sciences and Pollution Management Aerospace Database Copper Technical Reference Library Engineered Materials Abstracts Genetics Abstracts Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Chemoreception Abstracts Industrial and Applied Microbiology Abstracts (Microbiology A) Advanced Technologies Database with Aerospace ANTE: Abstracts in New Technology & Engineering Civil Engineering Abstracts Aluminium Industry Abstracts Virology and AIDS Abstracts Electronics & Communications Abstracts Ceramic Abstracts Ecology Abstracts Neurosciences Abstracts METADEX Biotechnology and BioEngineering Abstracts Computer and Information Systems Abstracts Professional Entomology Abstracts Animal Behavior Abstracts Solid State and Superconductivity Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts Corrosion Abstracts MEDLINE - Academic |
| DatabaseTitleList | MEDLINE CrossRef MEDLINE - Academic Materials Research Database |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Sciences (General) Biology |
| EISSN | 1095-9203 |
| ExternalDocumentID | PMC8118650 33632820 10_1126_science_abb8255 |
| Genre | Review Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIMH NIH HHS grantid: R01 MH115679 – fundername: NIA NIH HHS grantid: R56 AG060631 – fundername: NINDS NIH HHS grantid: UH3 NS100128 |
| GroupedDBID | --- --Z -DZ -ET -~X .-4 ..I .55 .DC 08G 0R~ 0WA 123 18M 2FS 2KS 2WC 2XV 34G 36B 39C 3R3 53G 5RE 66. 6OB 6TJ 7X2 7~K 85S 8F7 AABCJ AACGO AAIKC AAMNW AANCE AAWTO AAYXX ABCQX ABDBF ABDEX ABDQB ABEFU ABIVO ABJNI ABOCM ABPLY ABPPZ ABQIJ ABTLG ABWJO ABZEH ACBEA ACBEC ACGFO ACGFS ACGOD ACIWK ACMJI ACNCT ACPRK ACQOY ACUHS ADDRP ADUKH ADXHL AEGBM AENEX AETEA AFBNE AFFNX AFHKK AFQFN AFRAH AGFXO AGNAY AGSOS AHMBA AIDAL AIDUJ AJGZS ALIPV ALMA_UNASSIGNED_HOLDINGS ALSLI ASPBG AVWKF BKF BLC C45 CITATION CS3 DB2 DU5 EBS EMOBN F5P FA8 FEDTE HZ~ I.T IAO IEA IGS IH2 IHR INH INR IOF IOV IPO IPY ISE JCF JLS JSG JST K-O KCC L7B LSO LU7 M0P MQT MVM N9A NEJ NHB O9- OCB OFXIZ OGEVE OMK OVD P-O P2P PQQKQ PZZ RHI RXW SC5 SJN TAE TEORI TN5 TWZ UBW UCV UHB UKR UMD UNMZH UQL USG VVN WH7 WI4 X7M XJF XZL Y6R YK4 YKV YNT YOJ YR2 YR5 YRY YSQ YV5 YWH YYP YZZ ZCA ZE2 ~02 ~G0 ~KM ~ZZ CGR CUY CVF ECM EIF GX1 NPM OK1 UIG YCJ 7QF 7QG 7QL 7QP 7QQ 7QR 7SC 7SE 7SN 7SP 7SR 7SS 7T7 7TA 7TB 7TK 7TM 7U5 7U9 8BQ 8FD C1K F28 FR3 H8D H8G H94 JG9 JQ2 K9. KR7 L7M L~C L~D M7N P64 RC3 7X8 5PM |
| ID | FETCH-LOGICAL-c487t-2a2d2aabd2643f9fa7ba2f05d4b93dbd344580c242f5b1136e2db4d3ca3882153 |
| ISSN | 0036-8075 1095-9203 |
| IngestDate | Thu Aug 21 18:45:37 EDT 2025 Fri Jul 11 00:49:14 EDT 2025 Fri Jul 25 19:06:26 EDT 2025 Thu Apr 03 06:53:04 EDT 2025 Thu Apr 24 22:52:30 EDT 2025 Tue Jul 01 01:35:27 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6532 |
| Language | English |
| License | Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c487t-2a2d2aabd2643f9fa7ba2f05d4b93dbd344580c242f5b1136e2db4d3ca3882153 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 |
| ORCID | 0000-0001-5307-8264 0000-0001-6256-9559 0000-0003-1043-581X |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/8118650 |
| PMID | 33632820 |
| PQID | 2493564801 |
| PQPubID | 1256 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_8118650 proquest_miscellaneous_2494294173 proquest_journals_2493564801 pubmed_primary_33632820 crossref_citationtrail_10_1126_science_abb8255 crossref_primary_10_1126_science_abb8255 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2021-02-26 20210226 |
| PublicationDateYYYYMMDD | 2021-02-26 |
| PublicationDate_xml | – month: 02 year: 2021 text: 2021-02-26 day: 26 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Washington |
| PublicationTitle | Science (American Association for the Advancement of Science) |
| PublicationTitleAlternate | Science |
| PublicationYear | 2021 |
| Publisher | The American Association for the Advancement of Science |
| Publisher_xml | – name: The American Association for the Advancement of Science |
| References | e_1_3_1_118_2 e_1_3_1_81_2 e_1_3_1_137_2 e_1_3_1_114_2 e_1_3_1_133_2 e_1_3_1_110_2 e_1_3_1_43_2 e_1_3_1_66_2 e_1_3_1_89_2 e_1_3_1_140_2 e_1_3_1_24_2 e_1_3_1_62_2 e_1_3_1_85_2 e_1_3_1_20_2 e_1_3_1_6_2 e_1_3_1_47_2 e_1_3_1_2_2 e_1_3_1_28_2 e_1_3_1_106_2 e_1_3_1_129_2 e_1_3_1_70_2 e_1_3_1_93_2 e_1_3_1_102_2 e_1_3_1_148_2 e_1_3_1_125_2 e_1_3_1_144_2 e_1_3_1_121_2 e_1_3_1_32_2 e_1_3_1_78_2 e_1_3_1_151_2 e_1_3_1_13_2 e_1_3_1_51_2 e_1_3_1_74_2 e_1_3_1_97_2 e_1_3_1_17_2 e_1_3_1_36_2 e_1_3_1_59_2 e_1_3_1_119_2 e_1_3_1_115_2 e_1_3_1_138_2 e_1_3_1_80_2 e_1_3_1_111_2 e_1_3_1_134_2 e_1_3_1_141_2 e_1_3_1_65_2 e_1_3_1_23_2 e_1_3_1_46_2 e_1_3_1_88_2 e_1_3_1_7_2 e_1_3_1_61_2 e_1_3_1_42_2 e_1_3_1_84_2 e_1_3_1_3_2 e_1_3_1_69_2 e_1_3_1_27_2 e_1_3_1_107_2 e_1_3_1_103_2 e_1_3_1_126_2 e_1_3_1_149_2 e_1_3_1_92_2 e_1_3_1_122_2 e_1_3_1_145_2 e_1_3_1_54_2 e_1_3_1_35_2 e_1_3_1_77_2 e_1_3_1_12_2 e_1_3_1_50_2 e_1_3_1_96_2 e_1_3_1_31_2 e_1_3_1_73_2 e_1_3_1_16_2 e_1_3_1_58_2 e_1_3_1_39_2 e_1_3_1_139_2 e_1_3_1_116_2 e_1_3_1_60_2 e_1_3_1_135_2 e_1_3_1_112_2 e_1_3_1_131_2 e_1_3_1_22_2 e_1_3_1_45_2 e_1_3_1_68_2 e_1_3_1_87_2 e_1_3_1_8_2 e_1_3_1_41_2 e_1_3_1_64_2 e_1_3_1_83_2 e_1_3_1_4_2 e_1_3_1_26_2 e_1_3_1_49_2 e_1_3_1_108_2 e_1_3_1_127_2 e_1_3_1_91_2 e_1_3_1_104_2 e_1_3_1_146_2 e_1_3_1_123_2 e_1_3_1_100_2 e_1_3_1_142_2 e_1_3_1_130_2 e_1_3_1_34_2 e_1_3_1_57_2 e_1_3_1_76_2 e_1_3_1_99_2 e_1_3_1_11_2 e_1_3_1_30_2 e_1_3_1_53_2 e_1_3_1_72_2 e_1_3_1_95_2 e_1_3_1_15_2 e_1_3_1_19_2 e_1_3_1_38_2 e_1_3_1_117_2 e_1_3_1_82_2 e_1_3_1_113_2 e_1_3_1_136_2 Ke Y. D. (e_1_3_1_44_2) 2012; 2012 e_1_3_1_132_2 e_1_3_1_21_2 Cantero J. L. (e_1_3_1_55_2) 2011; 21 e_1_3_1_67_2 e_1_3_1_40_2 e_1_3_1_86_2 e_1_3_1_9_2 e_1_3_1_63_2 e_1_3_1_29_2 e_1_3_1_5_2 e_1_3_1_25_2 e_1_3_1_48_2 e_1_3_1_109_2 e_1_3_1_128_2 e_1_3_1_71_2 e_1_3_1_105_2 e_1_3_1_124_2 e_1_3_1_147_2 e_1_3_1_90_2 e_1_3_1_101_2 e_1_3_1_120_2 e_1_3_1_143_2 e_1_3_1_33_2 e_1_3_1_79_2 e_1_3_1_150_2 e_1_3_1_56_2 e_1_3_1_98_2 e_1_3_1_75_2 e_1_3_1_10_2 e_1_3_1_52_2 e_1_3_1_94_2 e_1_3_1_14_2 e_1_3_1_37_2 e_1_3_1_18_2 |
| References_xml | – ident: e_1_3_1_40_2 doi: 10.1126/science.1194653 – ident: e_1_3_1_138_2 doi: 10.1038/nature24016 – ident: e_1_3_1_83_2 doi: 10.1001/jama.2020.12134 – ident: e_1_3_1_17_2 doi: 10.3389/fneur.2013.00114 – ident: e_1_3_1_127_2 doi: 10.1385/JMN:17:2:225 – ident: e_1_3_1_32_2 doi: 10.1016/j.cub.2018.05.045 – ident: e_1_3_1_129_2 doi: 10.1126/science.1062097 – ident: e_1_3_1_134_2 doi: 10.1038/s41591-018-0004-z – ident: e_1_3_1_143_2 doi: 10.1056/NEJMoa1900907 – volume: 21 start-page: 827 year: 2011 ident: e_1_3_1_55_2 article-title: Role of tau protein on neocortical and hippocampal oscillatory patterns publication-title: Hippocampus doi: 10.1002/hipo.20798 – ident: e_1_3_1_97_2 doi: 10.1038/s41593-018-0298-7 – ident: e_1_3_1_136_2 doi: 10.1016/S0002-9440(10)64963-2 – ident: e_1_3_1_20_2 doi: 10.1186/s40478-017-0489-6 – ident: e_1_3_1_39_2 doi: 10.1083/jcb.201407065 – ident: e_1_3_1_62_2 doi: 10.1016/j.neurobiolaging.2014.05.001 – ident: e_1_3_1_80_2 doi: 10.1126/science.aah6205 – ident: e_1_3_1_21_2 doi: 10.1038/s41467-017-00618-0 – volume: 2012 year: 2012 ident: e_1_3_1_44_2 article-title: Lessons from tau-deficient mice publication-title: Int. J. Alzheimers Dis. – ident: e_1_3_1_63_2 doi: 10.1038/ng.2257 – ident: e_1_3_1_105_2 doi: 10.1523/JNEUROSCI.2369-17.2018 – ident: e_1_3_1_9_2 doi: 10.1074/jbc.M115.641902 – ident: e_1_3_1_6_2 doi: 10.1186/s13024-015-0025-8 – ident: e_1_3_1_130_2 doi: 10.1126/science.1058189 – ident: e_1_3_1_81_2 doi: 10.1001/jamaneurol.2020.0989 – ident: e_1_3_1_125_2 doi: 10.1016/j.neurobiolaging.2014.09.007 – ident: e_1_3_1_85_2 doi: 10.1038/s41593-017-0022-z – ident: e_1_3_1_96_2 doi: 10.1074/jbc.RA119.007527 – ident: e_1_3_1_151_2 doi: 10.7554/eLife.45457 – ident: e_1_3_1_71_2 doi: 10.1186/s40478-015-0210-6 – ident: e_1_3_1_113_2 doi: 10.1038/s41586-019-1769-z – ident: e_1_3_1_28_2 doi: 10.1523/JNEUROSCI.2107-13.2013 – ident: e_1_3_1_141_2 doi: 10.1016/j.neuron.2017.04.010 – ident: e_1_3_1_77_2 doi: 10.1038/s41591-020-0938-9 – ident: e_1_3_1_119_2 doi: 10.1038/embor.2013.15 – ident: e_1_3_1_46_2 doi: 10.1126/scitranslmed.aag0481 – ident: e_1_3_1_93_2 doi: 10.1093/brain/awv222 – ident: e_1_3_1_90_2 doi: 10.1101/gr.233866.117 – ident: e_1_3_1_104_2 doi: 10.1186/s13100-019-0176-1 – ident: e_1_3_1_49_2 doi: 10.1001/archneur.63.9.1312 – ident: e_1_3_1_112_2 doi: 10.1016/j.neuron.2018.10.031 – ident: e_1_3_1_35_2 doi: 10.1083/jcb.150.5.989 – ident: e_1_3_1_86_2 doi: 10.3389/fnins.2019.00659 – ident: e_1_3_1_87_2 doi: 10.1038/srep19393 – ident: e_1_3_1_23_2 doi: 10.1126/science.1141736 – ident: e_1_3_1_36_2 doi: 10.1523/JNEUROSCI.0188-12.2012 – ident: e_1_3_1_144_2 doi: 10.2174/15672050113109990143 – ident: e_1_3_1_149_2 doi: 10.1126/scitranslmed.aat3005 – ident: e_1_3_1_59_2 doi: 10.3389/fnins.2012.00104 – ident: e_1_3_1_26_2 doi: 10.1093/brain/awx005 – ident: e_1_3_1_123_2 doi: 10.1038/ncb1901 – ident: e_1_3_1_147_2 doi: 10.1016/j.neurobiolaging.2011.10.020 – ident: e_1_3_1_114_2 doi: 10.1523/JNEUROSCI.4361-12.2013 – ident: e_1_3_1_116_2 doi: 10.1084/jem.20190980 – ident: e_1_3_1_66_2 doi: 10.1093/brain/awy117 – ident: e_1_3_1_3_2 doi: 10.1091/mbc.e14-06-1099 – ident: e_1_3_1_14_2 doi: 10.1523/JNEUROSCI.23-18-06972.2003 – ident: e_1_3_1_139_2 doi: 10.1186/s40478-019-0664-z – ident: e_1_3_1_64_2 doi: 10.1073/pnas.91.12.5562 – ident: e_1_3_1_91_2 doi: 10.1016/j.neuron.2018.02.015 – ident: e_1_3_1_150_2 doi: 10.1016/j.cell.2019.11.031 – ident: e_1_3_1_132_2 doi: 10.1172/JCI137040 – ident: e_1_3_1_30_2 doi: 10.1021/bi00035a017 – ident: e_1_3_1_126_2 doi: 10.1186/1750-1326-9-43 – ident: e_1_3_1_51_2 doi: 10.1016/j.neurobiolaging.2014.05.005 – ident: e_1_3_1_140_2 doi: 10.1038/s41582-018-0013-z – ident: e_1_3_1_25_2 doi: 10.1038/s41588-018-0311-9 – ident: e_1_3_1_69_2 doi: 10.1093/brain/aww187 – ident: e_1_3_1_131_2 doi: 10.1073/pnas.092136199 – ident: e_1_3_1_95_2 doi: 10.1038/nrn2055 – ident: e_1_3_1_12_2 doi: 10.1007/978-981-32-9358-8_28 – ident: e_1_3_1_24_2 doi: 10.1038/s41588-019-0358-2 – ident: e_1_3_1_111_2 doi: 10.1016/j.celrep.2018.07.072 – ident: e_1_3_1_2_2 doi: 10.1038/nrn.2015.1 – ident: e_1_3_1_53_2 doi: 10.1098/rstb.2013.0144 – ident: e_1_3_1_65_2 doi: 10.1126/scitranslmed.aau5732 – ident: e_1_3_1_10_2 doi: 10.1038/nn.4067 – ident: e_1_3_1_121_2 doi: 10.1007/s00401-014-1254-6 – ident: e_1_3_1_56_2 doi: 10.3233/JAD-2010-100285 – ident: e_1_3_1_58_2 doi: 10.1016/j.smrv.2014.03.007 – ident: e_1_3_1_88_2 doi: 10.1186/s13024-017-0231-7 – ident: e_1_3_1_8_2 doi: 10.1371/journal.pone.0084849 – ident: e_1_3_1_124_2 doi: 10.1523/JNEUROSCI.1590-19.2019 – ident: e_1_3_1_106_2 doi: 10.1186/s13024-019-0354-0 – ident: e_1_3_1_18_2 doi: 10.1038/nm.4199 – ident: e_1_3_1_68_2 doi: 10.1016/S2352-3018(20)30069-2 – ident: e_1_3_1_48_2 doi: 10.1016/j.nbd.2019.01.008 – ident: e_1_3_1_75_2 doi: 10.1016/j.cell.2012.02.046 – ident: e_1_3_1_79_2 doi: 10.1016/j.sbi.2020.05.011 – ident: e_1_3_1_37_2 doi: 10.1523/JNEUROSCI.4922-11.2012 – ident: e_1_3_1_109_2 doi: 10.1016/j.neuron.2016.03.005 – ident: e_1_3_1_89_2 doi: 10.1038/s41467-019-10428-1 – ident: e_1_3_1_16_2 doi: 10.1007/978-981-32-9358-8_1 – ident: e_1_3_1_43_2 doi: 10.1016/j.neurobiolaging.2012.12.003 – ident: e_1_3_1_76_2 doi: 10.1038/nature20587 – ident: e_1_3_1_84_2 doi: 10.1038/s41582-020-0348-0 – ident: e_1_3_1_94_2 doi: 10.1016/j.neuron.2018.01.022 – ident: e_1_3_1_78_2 doi: 10.1016/j.neuron.2016.09.055 – ident: e_1_3_1_31_2 doi: 10.1083/jcb.103.6.2739 – ident: e_1_3_1_137_2 doi: 10.1523/JNEUROSCI.4040-10.2010 – ident: e_1_3_1_54_2 doi: 10.1016/j.neuron.2009.05.012 – ident: e_1_3_1_67_2 doi: 10.1126/science.1113694 – ident: e_1_3_1_128_2 doi: 10.1186/s13024-019-0306-8 – ident: e_1_3_1_41_2 doi: 10.1523/JNEUROSCI.5242-07.2008 – ident: e_1_3_1_70_2 doi: 10.15252/embr.201541438 – ident: e_1_3_1_146_2 doi: 10.1016/j.stem.2018.12.013 – ident: e_1_3_1_47_2 doi: 10.1084/jem.20161731 – ident: e_1_3_1_15_2 doi: 10.1038/s41586-019-1688-z – ident: e_1_3_1_117_2 doi: 10.1038/s41586-020-2156-5 – ident: e_1_3_1_103_2 doi: 10.1186/s40478-019-0723-5 – ident: e_1_3_1_115_2 doi: 10.1016/j.cell.2012.02.040 – ident: e_1_3_1_92_2 doi: 10.1016/j.stemcr.2017.06.005 – ident: e_1_3_1_33_2 doi: 10.1038/369488a0 – ident: e_1_3_1_82_2 doi: 10.1038/s41591-020-0781-z – ident: e_1_3_1_110_2 doi: 10.1186/s40478-019-0754-y – ident: e_1_3_1_148_2 doi: 10.1016/j.neuron.2010.08.044 – ident: e_1_3_1_118_2 doi: 10.1001/jamaneurol.2018.2505 – ident: e_1_3_1_120_2 doi: 10.1038/nn.4328 – ident: e_1_3_1_29_2 doi: 10.1091/mbc.6.12.1887 – ident: e_1_3_1_5_2 doi: 10.1016/j.neuron.2018.06.003 – ident: e_1_3_1_19_2 doi: 10.1016/j.neuron.2020.01.038 – ident: e_1_3_1_135_2 doi: 10.1523/JNEUROSCI.4315-03.2004 – ident: e_1_3_1_108_2 doi: 10.1016/j.neuron.2019.08.008 – ident: e_1_3_1_50_2 doi: 10.1016/j.ajpath.2013.11.021 – ident: e_1_3_1_52_2 doi: 10.1523/JNEUROSCI.4152-10.2011 – ident: e_1_3_1_133_2 doi: 10.1523/JNEUROSCI.2552-14.2015 – ident: e_1_3_1_142_2 doi: 10.1056/NEJMoa1710504 – ident: e_1_3_1_42_2 doi: 10.1016/j.nbd.2018.05.020 – ident: e_1_3_1_145_2 doi: 10.1021/jacs.0c00768 – ident: e_1_3_1_98_2 doi: 10.1111/acel.12692 – ident: e_1_3_1_73_2 doi: 10.31887/DCNS.2012.14.4/gbuzsaki – ident: e_1_3_1_22_2 doi: 10.1002/ana.24230 – ident: e_1_3_1_72_2 doi: 10.1016/j.nbd.2013.06.005 – ident: e_1_3_1_57_2 doi: 10.1126/science.aav2546 – ident: e_1_3_1_101_2 doi: 10.1038/s41593-018-0194-1 – ident: e_1_3_1_38_2 doi: 10.1016/j.neulet.2020.134919 – ident: e_1_3_1_45_2 doi: 10.1016/j.cell.2010.06.036 – ident: e_1_3_1_11_2 doi: 10.1021/acs.analchem.5b04509 – ident: e_1_3_1_61_2 doi: 10.1038/nm.2613 – ident: e_1_3_1_13_2 doi: 10.1016/j.conb.2018.04.027 – ident: e_1_3_1_100_2 doi: 10.1038/nm.4011 – ident: e_1_3_1_7_2 doi: 10.1074/jbc.M117.784702 – ident: e_1_3_1_34_2 doi: 10.1523/JNEUROSCI.3439-13.2014 – ident: e_1_3_1_74_2 doi: 10.1016/j.neurobiolaging.2017.05.017 – ident: e_1_3_1_122_2 doi: 10.1523/JNEUROSCI.2642-12.2013 – ident: e_1_3_1_4_2 doi: 10.1084/jem.20131685 – ident: e_1_3_1_60_2 doi: 10.1093/hmg/ddr603 – ident: e_1_3_1_102_2 doi: 10.1016/j.celrep.2018.05.004 – ident: e_1_3_1_27_2 doi: 10.1093/hmg/dds161 – ident: e_1_3_1_99_2 doi: 10.1038/s41580-019-0101-y – ident: e_1_3_1_107_2 doi: 10.1007/s00401-017-1674-1 |
| SSID | ssj0009593 |
| Score | 2.6547432 |
| SecondaryResourceType | review_article |
| Snippet | The protein tau is implicated in several brain disorders, including Alzheimer's disease, suggesting that it could be a target of therapeutics. However, because... Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer's disease, other neurodegenerative... The many faces of tauThe protein tau is implicated in several brain disorders, including Alzheimer's disease, suggesting that it could be a target of... Several lines of evidence implicate the protein tau in the pathogenesis of multiple brain disorders, including Alzheimer’s disease, other neurodegenerative... |
| SourceID | pubmedcentral proquest pubmed crossref |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source |
| SubjectTerms | Ablation Abnormalities Agglomeration Aging Aging (Individuals) Alternative splicing Alzheimer's disease Animals Antisense oligonucleotides Antisense therapy Autism Axonal transport Barriers Biological activity Biomarkers Brain Brain - physiology Brain diseases Brain Diseases - metabolism Brain Diseases - therapy Complexity Drug development Epilepsy Humans Inclusions Internalization Isoforms Microtubule-associated proteins Microtubules - metabolism Neural networks Neurodegenerative diseases Neurodevelopmental disorders Neurons - physiology Oligonucleotides Pathogenesis Pathology Pragmatics Proteins Reduction Seeds Semiotics Signaling Splicing Survival Synapses Synaptogenesis Tau protein tau Proteins - chemistry tau Proteins - genetics tau Proteins - metabolism Tauopathies - metabolism Tauopathies - therapy |
| Title | Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/33632820 https://www.proquest.com/docview/2493564801 https://www.proquest.com/docview/2494294173 https://pubmed.ncbi.nlm.nih.gov/PMC8118650 |
| Volume | 371 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Na9swFBdZymCXsXYf9dYNDXboCA62JNvxbmmWUEbWXRKWy_AkSyaB4pTGGXR__Z4syXHaDrpdTLDlKOT309N7T-8DoQ8JT1UM24Yfpkr4LOTCT0Et9dOCBSpVjBWxznf-ehGfz9mXRbTodH62opa2lejnv-_NK_kfVOEe4KqzZP8B2eZL4QZ8BnzhCgjD9WEY86226Md1_lPt7pd1mIXqCd35QZ--1KU1TR1mE_StR13zq5W8vOkpkE2_bL6Uy8LqbSpXPaKtuDoZAAppc8jTgraJVhyamAIXYmBfa_kbRs5DPVoq_7taNS6eJV87wbxjQW5ih6awHbhqTNZFQcI65TtuSdVAN4QkgZFk6p57VhRT047Fci6OjOvzrpRv9aVUfS4EmLnRbkNzh_gX37LJfDrNZuPF7BE6IGBIkC46GJ59PpvcLszc_Bxb_qmVWOUm2Ndc7pgjt6NqW2rK7Bl6au0LPDRkOUQdVR6hx6bj6M0ROrSAbPCpLTj-8Tn6ATz6hC2L8LrAlkW4ZhFuWISBRdiwSI-yLMKORbjFIrxj0Qs0n4xno3Pftt3wc7BeK59wIgnnQoKuTIu04IngpAgiyURKpZCUsWgQ5KDbFZHQLYEUkYJJmnMK5hrsoC9Rt1yX6hhhML5zzlN99gyrPk8GMgxjQSIJVkkKeHio7_7SLLc16XVrlMustk1JnFkMMouBh06bF65MOZa_Dz1xGGV2zW4ywlIaxbpkkofeN49BoupjMl6q9bYeA0oaCxPqoVcG0mYuSmNKQGn2ULIHdjNAV2vff1KulnXV9gGY8mAOvX7AvG_Qk90yOkHd6nqr3oLuW4l3lr5_ABswtg8 |
| linkProvider | EBSCOhost |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Tau%3A+Enabler+of+diverse+brain+disorders+and+target+of+rapidly+evolving+therapeutic+strategies&rft.jtitle=Science+%28American+Association+for+the+Advancement+of+Science%29&rft.au=Chang%2C+Che-Wei&rft.au=Shao%2C+Eric&rft.au=Mucke%2C+Lennart&rft.date=2021-02-26&rft.issn=1095-9203&rft.eissn=1095-9203&rft.volume=371&rft.issue=6532&rft_id=info:doi/10.1126%2Fscience.abb8255&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0036-8075&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0036-8075&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0036-8075&client=summon |