Small-molecule activation of lysosomal TRP channels ameliorates Duchenne muscular dystrophy in mouse models
Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca channel required for lysosomal exocytosis, produce...
Saved in:
| Published in | Science advances Vol. 6; no. 6; p. eaaz2736 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Association for the Advancement of Science (AAAS)
07.02.2020
American Association for the Advancement of Science |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca
channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of
mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca
channels may represent a promising approach to treat DMD and related muscle diseases. |
|---|---|
| AbstractList | Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca
channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of
mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca
channels may represent a promising approach to treat DMD and related muscle diseases. A lysosome activator ameliorates muscular dystrophies. Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca 2+ channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of mdx mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca 2+ channels may represent a promising approach to treat DMD and related muscle diseases. Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca 2+ channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of mdx mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca 2+ channels may represent a promising approach to treat DMD and related muscle diseases. A lysosome activator ameliorates muscular dystrophies. Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca 2+ channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of mdx mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca 2+ channels may represent a promising approach to treat DMD and related muscle diseases. |
| Author | Li, Dan Tang, Kaiyuan Yang, Yexin Martinez, Natalia J Zhang, Xiaoli Davis, Carol S Calvo, Raul Marugan, Juan Wang, Ce Sahoo, Nirakar Ferrer, Marc He, Wanwan Zhao, Zifan Bigot, Anne Southall, Noel Yu, Lu Converso-Baran, Kimber Xu, Haoxing Brooks, Susan V Hu, Xin |
| Author_xml | – sequence: 1 givenname: Lu orcidid: 0000-0002-6972-6489 surname: Yu fullname: Yu, Lu organization: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA – sequence: 2 givenname: Xiaoli orcidid: 0000-0002-0507-6317 surname: Zhang fullname: Zhang, Xiaoli organization: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA – sequence: 3 givenname: Yexin surname: Yang fullname: Yang, Yexin organization: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA – sequence: 4 givenname: Dan surname: Li fullname: Li, Dan organization: Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China – sequence: 5 givenname: Kaiyuan surname: Tang fullname: Tang, Kaiyuan organization: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA – sequence: 6 givenname: Zifan surname: Zhao fullname: Zhao, Zifan organization: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA – sequence: 7 givenname: Wanwan surname: He fullname: He, Wanwan organization: Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China – sequence: 8 givenname: Ce orcidid: 0000-0003-1932-0218 surname: Wang fullname: Wang, Ce organization: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA – sequence: 9 givenname: Nirakar orcidid: 0000-0003-0669-3840 surname: Sahoo fullname: Sahoo, Nirakar organization: Department of Biology, The University of Texas Rio Grande Valley, 1201 W University Dr., Edinburg, TX 78539, USA – sequence: 10 givenname: Kimber orcidid: 0000-0002-5436-5836 surname: Converso-Baran fullname: Converso-Baran, Kimber organization: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA – sequence: 11 givenname: Carol S surname: Davis fullname: Davis, Carol S organization: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA – sequence: 12 givenname: Susan V orcidid: 0000-0003-1954-967X surname: Brooks fullname: Brooks, Susan V organization: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA – sequence: 13 givenname: Anne orcidid: 0000-0003-0337-5425 surname: Bigot fullname: Bigot, Anne organization: Sorbonne Université, INSERM, AIM, Center for Research in Myology, UMRS974, GH Pitié-Salpétrière, 75651 Paris Cedex 13, France – sequence: 14 givenname: Raul surname: Calvo fullname: Calvo, Raul organization: NIH/NCATS/NCGC, 9800 Medical Center Drive, Rockville, MD 20850, USA – sequence: 15 givenname: Natalia J surname: Martinez fullname: Martinez, Natalia J organization: NIH/NCATS/NCGC, 9800 Medical Center Drive, Rockville, MD 20850, USA – sequence: 16 givenname: Noel orcidid: 0000-0003-4500-880X surname: Southall fullname: Southall, Noel organization: NIH/NCATS/NCGC, 9800 Medical Center Drive, Rockville, MD 20850, USA – sequence: 17 givenname: Xin surname: Hu fullname: Hu, Xin organization: NIH/NCATS/NCGC, 9800 Medical Center Drive, Rockville, MD 20850, USA – sequence: 18 givenname: Juan orcidid: 0000-0002-3951-7061 surname: Marugan fullname: Marugan, Juan organization: NIH/NCATS/NCGC, 9800 Medical Center Drive, Rockville, MD 20850, USA – sequence: 19 givenname: Marc surname: Ferrer fullname: Ferrer, Marc organization: NIH/NCATS/NCGC, 9800 Medical Center Drive, Rockville, MD 20850, USA – sequence: 20 givenname: Haoxing orcidid: 0000-0003-3561-4654 surname: Xu fullname: Xu, Haoxing organization: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building, 1105 North University, Ann Arbor, MI 48109, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32128386$$D View this record in MEDLINE/PubMed https://hal.sorbonne-universite.fr/hal-02493967$$DView record in HAL |
| BookMark | eNpdkc1v1DAQxS1URD_olSPyEQ5Z_O3kglQVSpFWAkE5W7OOQwyOvdjJSstfj6tdqsJpRjPvvdHod45OYooOoReUrChl6k2xHvrdCuA301w9QWeMa9kwKdqTR_0puizlByGECqUk7Z6hU84oa3mrztDPrxOE0EwpOLsEh8HOfgezTxGnAYd9SSVVBb778hnbEWJ0oWCYXPApw-wKfrfY0dUxnpZSEyDjfl_mnLbjHvuIp7SUukt99T1HTwcIxV0e6wX6dvP-7vq2WX_68PH6at1YwcTcDC3vJAeuhbIbsBI6R0Sv2bBhVIqBkn6jekfkoCXR1HZaMZBMt4KQVlgi-QV6e8jdLpvJ9dbFOUMw2-wnyHuTwJt_N9GP5nvaGU046xivAa8PAeN_tturtbmfESY63im9o1X76ngsp1-LK7OZfLEuBIiu_m4qBkoFV7Kr0tVBanMqJbvhIZsScw_UHICaI9BqePn4kQf5X3z8D-lToYQ |
| CitedBy_id | crossref_primary_10_1016_j_ceca_2022_102597 crossref_primary_10_1016_j_bmcl_2023_129595 crossref_primary_10_1080_21505594_2024_2350893 crossref_primary_10_1093_hmg_ddab278 crossref_primary_10_3390_ijms25126565 crossref_primary_10_1016_j_bbamcr_2022_119386 crossref_primary_10_1038_s41598_021_87817_4 crossref_primary_10_1073_pnas_2318412121 crossref_primary_10_1080_15548627_2021_2008752 crossref_primary_10_1016_j_ymthe_2023_06_018 crossref_primary_10_1007_s00415_023_11796_x crossref_primary_10_1038_s41598_024_51746_9 crossref_primary_10_1016_j_nmd_2020_12_009 crossref_primary_10_1083_jcb_202109133 crossref_primary_10_1152_physrev_00025_2023 crossref_primary_10_1161_CIRCRESAHA_120_317567 crossref_primary_10_1038_s43587_024_00614_2 crossref_primary_10_1007_s12015_022_10384_2 crossref_primary_10_1038_s41580_023_00676_x crossref_primary_10_3389_fphys_2021_647010 crossref_primary_10_1016_j_celrep_2021_109848 crossref_primary_10_3390_ijms25010458 crossref_primary_10_1002_sctm_21_0054 crossref_primary_10_1016_j_pharmthera_2020_107713 crossref_primary_10_1080_15548627_2024_2333715 crossref_primary_10_3389_fonc_2023_1326023 crossref_primary_10_14336_AD_2022_0927 crossref_primary_10_1146_annurev_pharmtox_051921_013755 crossref_primary_10_1172_jci_insight_164768 crossref_primary_10_12677_ACM_2021_116381 |
| Cites_doi | 10.1038/ncb0109-7 10.1242/jcs.106.1.121 10.4155/fmc.09.140 10.1038/nrm2024 10.1126/scitranslmed.aan8081 10.1186/2044-5040-1-34 10.1016/S0140-6736(12)61897-2 10.1083/jcb.201212142 10.1002/mus.880030405 10.1073/pnas.1419669112 10.1113/jphysiol.1996.sp021790 10.1007/s00018-012-1248-2 10.1152/ajpregu.00093.2011 10.1152/japplphysiol.01026.2003 10.1016/j.nmd.2004.04.007 10.1152/ajpregu.00454.2004 10.1016/j.semcdb.2015.10.031 10.1152/physrev.00007.2015 10.1016/j.devcel.2017.04.003 10.1038/ncb3114 10.1016/j.nmd.2011.07.008 10.1083/jcb.139.2.375 10.1038/ncomms1735 10.1002/emmm.201202176 10.1038/ncomms5425 10.1016/j.devcel.2013.08.003 10.1242/jcs.190322 10.1038/ncomms1037 10.1093/hmg/ddh174 10.1038/ncomms12109 10.1146/annurev-physiol-021014-071649 10.1016/j.devcel.2011.07.016 10.1038/nm.3611 10.1016/0092-8674(95)90344-5 10.1016/j.tibs.2018.10.006 10.1038/ncb1812 10.1016/j.ymthe.2017.03.022 10.1016/S1097-2765(00)80155-0 10.1016/S0092-8674(00)80533-4 10.1038/nature07311 10.1038/nature01573 10.1038/352536a0 10.1073/pnas.1013077107 10.1083/jcb.200708010 |
| ContentType | Journal Article |
| Copyright | Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Distributed under a Creative Commons Attribution 4.0 International License Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2020 The Authors |
| Copyright_xml | – notice: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). – notice: Distributed under a Creative Commons Attribution 4.0 International License – notice: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2020 The Authors |
| DBID | NPM AAYXX CITATION 7X8 1XC VOOES 5PM |
| DOI | 10.1126/sciadv.aaz2736 |
| DatabaseName | PubMed CrossRef MEDLINE - Academic Hyper Article en Ligne (HAL) Hyper Article en Ligne (HAL) (Open Access) PubMed Central (Full Participant titles) |
| DatabaseTitle | PubMed CrossRef MEDLINE - Academic |
| DatabaseTitleList | PubMed CrossRef |
| 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 |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Sciences (General) |
| EISSN | 2375-2548 |
| EndPage | eaaz2736 |
| ExternalDocumentID | oai_HAL_hal_02493967v1 10_1126_sciadv_aaz2736 32128386 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIAMS NIH HHS grantid: P30 AR069620 – fundername: NINDS NIH HHS grantid: R01 NS062792 – fundername: NIAMS NIH HHS grantid: R01 AR060837 – fundername: NIDDK NIH HHS grantid: R01 DK115474 – fundername: ; grantid: AR069620 – fundername: ; grantid: DK115474 – fundername: ; grantid: AR060837 – fundername: ; grantid: NS062792 |
| GroupedDBID | 53G 5VS AAFWJ ACGFS ADAXU ADBBV ADPDF ADRAZ AENVI ALMA_UNASSIGNED_HOLDINGS AOIJS BBORY BCGUY BCNDV BKF EBS EJD FRP GROUPED_DOAJ HYE KQ8 M48 M~E NPM OK1 OVD OVEED RHF RHI RPM TEORI AAYXX AFPKN CITATION 7X8 1XC VOOES 5PM |
| ID | FETCH-LOGICAL-c424t-f83953a3746cbac5a9e04d72fb2154f10db6de05f75071c9762a527840084c053 |
| IEDL.DBID | RPM |
| ISSN | 2375-2548 |
| IngestDate | Tue Apr 09 21:54:25 EDT 2024 Tue Oct 15 15:51:25 EDT 2024 Thu Apr 11 19:00:17 EDT 2024 Thu Sep 12 20:43:40 EDT 2024 Wed Oct 16 00:46:49 EDT 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6 |
| Language | English |
| License | Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c424t-f83953a3746cbac5a9e04d72fb2154f10db6de05f75071c9762a527840084c053 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0003-0669-3840 0000-0003-1932-0218 0000-0002-5436-5836 0000-0002-0507-6317 0000-0002-6972-6489 0000-0003-3561-4654 0000-0003-1954-967X 0000-0003-4500-880X 0000-0002-3951-7061 0000-0003-0337-5425 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032923/ |
| PMID | 32128386 |
| PQID | 2371143659 |
| PQPubID | 23479 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_7032923 hal_primary_oai_HAL_hal_02493967v1 proquest_miscellaneous_2371143659 crossref_primary_10_1126_sciadv_aaz2736 pubmed_primary_32128386 |
| PublicationCentury | 2000 |
| PublicationDate | 2020-02-07 |
| PublicationDateYYYYMMDD | 2020-02-07 |
| PublicationDate_xml | – month: 02 year: 2020 text: 2020-02-07 day: 07 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Science advances |
| PublicationTitleAlternate | Sci Adv |
| PublicationYear | 2020 |
| Publisher | American Association for the Advancement of Science (AAAS) American Association for the Advancement of Science |
| Publisher_xml | – name: American Association for the Advancement of Science (AAAS) – name: American Association for the Advancement of Science |
| References | e_1_3_2_26_2 e_1_3_2_27_2 e_1_3_2_28_2 e_1_3_2_29_2 e_1_3_2_41_2 e_1_3_2_20_2 Kilpatrick B. S. (e_1_3_2_37_2) 2016; 129 e_1_3_2_43_2 e_1_3_2_21_2 e_1_3_2_42_2 e_1_3_2_22_2 e_1_3_2_45_2 e_1_3_2_23_2 e_1_3_2_44_2 e_1_3_2_24_2 e_1_3_2_25_2 e_1_3_2_46_2 e_1_3_2_9_2 e_1_3_2_15_2 e_1_3_2_38_2 e_1_3_2_8_2 e_1_3_2_16_2 e_1_3_2_7_2 e_1_3_2_17_2 e_1_3_2_6_2 e_1_3_2_18_2 e_1_3_2_39_2 e_1_3_2_19_2 e_1_3_2_30_2 e_1_3_2_32_2 e_1_3_2_10_2 e_1_3_2_31_2 e_1_3_2_5_2 e_1_3_2_11_2 e_1_3_2_34_2 e_1_3_2_4_2 e_1_3_2_12_2 e_1_3_2_33_2 e_1_3_2_3_2 e_1_3_2_13_2 e_1_3_2_36_2 e_1_3_2_2_2 e_1_3_2_14_2 e_1_3_2_35_2 Springer M. L. (e_1_3_2_40_2) 2002; 13 |
| References_xml | – ident: e_1_3_2_11_2 doi: 10.1038/ncb0109-7 – ident: e_1_3_2_18_2 doi: 10.1242/jcs.106.1.121 – ident: e_1_3_2_12_2 doi: 10.4155/fmc.09.140 – ident: e_1_3_2_3_2 doi: 10.1038/nrm2024 – ident: e_1_3_2_8_2 doi: 10.1126/scitranslmed.aan8081 – volume: 13 start-page: Unit13.4 year: 2002 ident: e_1_3_2_40_2 article-title: Gene delivery to muscle publication-title: Curr. Protoc. Hum. Genet. contributor: fullname: Springer M. L. – ident: e_1_3_2_46_2 doi: 10.1186/2044-5040-1-34 – ident: e_1_3_2_2_2 doi: 10.1016/S0140-6736(12)61897-2 – ident: e_1_3_2_4_2 doi: 10.1083/jcb.201212142 – ident: e_1_3_2_23_2 doi: 10.1002/mus.880030405 – ident: e_1_3_2_25_2 doi: 10.1073/pnas.1419669112 – ident: e_1_3_2_28_2 doi: 10.1113/jphysiol.1996.sp021790 – ident: e_1_3_2_31_2 doi: 10.1007/s00018-012-1248-2 – ident: e_1_3_2_43_2 doi: 10.1152/ajpregu.00093.2011 – ident: e_1_3_2_44_2 doi: 10.1152/japplphysiol.01026.2003 – ident: e_1_3_2_22_2 doi: 10.1016/j.nmd.2004.04.007 – ident: e_1_3_2_32_2 doi: 10.1152/ajpregu.00454.2004 – ident: e_1_3_2_26_2 doi: 10.1016/j.semcdb.2015.10.031 – ident: e_1_3_2_5_2 doi: 10.1152/physrev.00007.2015 – ident: e_1_3_2_16_2 doi: 10.1016/j.devcel.2017.04.003 – ident: e_1_3_2_33_2 doi: 10.1038/ncb3114 – ident: e_1_3_2_27_2 doi: 10.1016/j.nmd.2011.07.008 – ident: e_1_3_2_20_2 doi: 10.1083/jcb.139.2.375 – ident: e_1_3_2_13_2 doi: 10.1038/ncomms1735 – ident: e_1_3_2_15_2 doi: 10.1002/emmm.201202176 – ident: e_1_3_2_30_2 doi: 10.1038/ncomms5425 – ident: e_1_3_2_36_2 doi: 10.1016/j.devcel.2013.08.003 – volume: 129 start-page: 3859 year: 2016 ident: e_1_3_2_37_2 article-title: Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx publication-title: J. Cell Sci. doi: 10.1242/jcs.190322 contributor: fullname: Kilpatrick B. S. – ident: e_1_3_2_42_2 doi: 10.1038/ncomms1037 – ident: e_1_3_2_45_2 doi: 10.1093/hmg/ddh174 – ident: e_1_3_2_19_2 doi: 10.1038/ncomms12109 – ident: e_1_3_2_29_2 doi: 10.1146/annurev-physiol-021014-071649 – ident: e_1_3_2_35_2 doi: 10.1016/j.devcel.2011.07.016 – ident: e_1_3_2_14_2 doi: 10.1038/nm.3611 – ident: e_1_3_2_6_2 doi: 10.1016/0092-8674(95)90344-5 – ident: e_1_3_2_39_2 doi: 10.1016/j.tibs.2018.10.006 – ident: e_1_3_2_10_2 doi: 10.1038/ncb1812 – ident: e_1_3_2_34_2 doi: 10.1016/j.ymthe.2017.03.022 – ident: e_1_3_2_17_2 doi: 10.1016/S1097-2765(00)80155-0 – ident: e_1_3_2_21_2 doi: 10.1016/S0092-8674(00)80533-4 – ident: e_1_3_2_41_2 doi: 10.1038/nature07311 – ident: e_1_3_2_9_2 doi: 10.1038/nature01573 – ident: e_1_3_2_7_2 doi: 10.1038/352536a0 – ident: e_1_3_2_24_2 doi: 10.1073/pnas.1013077107 – ident: e_1_3_2_38_2 doi: 10.1083/jcb.200708010 |
| SSID | ssj0001466519 |
| Score | 2.3386407 |
| Snippet | Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no... A lysosome activator ameliorates muscular dystrophies. Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that... |
| SourceID | pubmedcentral hal proquest crossref pubmed |
| SourceType | Open Access Repository Aggregation Database Index Database |
| StartPage | eaaz2736 |
| SubjectTerms | Biochemistry, Molecular Biology Cell Biology Diseases and Disorders Human health and pathology Life Sciences SciAdv r-articles |
| SummonAdditionalLinks | – databaseName: Scholars Portal Open Access Journals dbid: M48 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1LT-MwELZ4XLiseC3bXUAGIe1yCAqOH8lhhRBQVQjQClqpt8h2HIE2TdimRXR_PTNJeJRy4GpHduJvnPnGngcheyq10tfO94CKM4-HifVM6DCAWWG2utTXBoOTL69kp8fP-6L_6v_ULGD5oWmH9aR6w-zg8d_kCDb87zcBMDp5OND6P-hiOU8WGQcrHd34GqpfnbdwKUVV54MFSnhgF4VNDsfZIaZ01PwtekjO0s_3XpRv1FJ7mXxp-CQ9rgVghcy5fJWsNDu2pL-atNL7a-TvzUBnmTeo6-E6ihEN9XksLVKaTcqiLOAJ2r3-QzEcOAetSfXAZRjED4SUno4BYGimg3HtvUqTSTkaFgAUvcspniFAH1bWKddJr33WPel4TakFz3LGR14KPEkEOlBcWqOt0JHzeaJYaoAS8PTQT4xMnC9ShfzRAodhWuCdJebjt7CRv5KFvMjdN0J9a5QxjCVSWh6lUhsQBxmoCGh8KGTSIj-fFze-rzNqxJUlwmRcwxA3MLTILqz9y0OYCLtzfBFjGyY6DCKpHg5bZOcZmhh2Bl536NzBF8eAMxh7gRRRi2zUUL2MFYDGDoMQplBTIE5NNt2T391W2bfhF8lAir9_5uV-kCWG9jl6eatNsjAajt0WkJiR2a6k8wn9OPOA priority: 102 providerName: Scholars Portal |
| Title | Small-molecule activation of lysosomal TRP channels ameliorates Duchenne muscular dystrophy in mouse models |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32128386 https://search.proquest.com/docview/2371143659 https://hal.sorbonne-universite.fr/hal-02493967 https://pubmed.ncbi.nlm.nih.gov/PMC7032923 |
| Volume | 6 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwEB6xnLhUQFtIW5BbVSocshscx06OiBatKrZCPCRuke04YtU8ENlFor--M3mgXXrrJQfbcRJ_48w39swY4KvKrQy0C3yk4twXcWZ9EzsKYFaUrS4PtKHg5NkvOb0VP--iuw2IhliY1mnfmvm4KspxNb9vfSsfSjsZ_MQml7MzlFKOHU1GMEIBXTHR24UVISXSkj5BYx8go7OnsdZ_UFfTmUUh_q_jkMKnV3TR6J48If-lma-9JVfUz_k2vOl5Izvt3m8HNly1Czv9zGzYUZ8--vgt_L4udVH4ZXfurWMUudCtu7I6Z8VzUzc1tmA3V5eMwn4r1I5Ml66gYH0knuz7EoHEYlYuOy9Vlj03i8caAWHzitFaAdbRCTrNO7g9_3FzNvX7IxV8K7hY-DnyoSjUoRLSGm0jnbhAZIrnBlW_yE-CzMjMBVGuiCda5CpcR7Q3SXn3LU7Y97BZ1ZXbBxZYo4zhPJPSiiSX2iDsMlQJ0vU4kpkH34bBTR-6zBlpa3FwmXaIpD0iHnzBsX9pRAmvp6cXKZVRQsMwkerpxIPPAzQpzgDa1tCVwy9OeajQqAtllHiw10H10teAtAdqDcS1h63XoNC1WbZ7Ifvw33d-hC1Oxjm5eKtPsLl4XLoDZDALc9ha_nidifiwld6_HQb2Vg |
| link.rule.ids | 230,315,730,783,787,867,888,24330,27936,27937,53804,53806 |
| linkProvider | National Library of Medicine |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB615QAXSnmG8jAICTgkmzqJvTlWhWqB3aqCLeotsh1HXTWPqslWan89M3lUu-UEVztxYs3Y88145jPAB5kZ4SvruwjFuRuOU-PqsaUCZklsdZmvNBUnz47E5CT8fhqdbkA01MK0SftGL7wyL7xycdbmVl4UZjTkiY2OZweopRwHGm3CPVyvfrjipLehlVAIBCY9RWNfIqPSK0-pG7TWdGtRgDv2OKAC6hVrtHlGuZB_A827-ZIrBuhwG34Pv97lnZx7y0Z75uYOq-M_z-0RPOwhKdvvundgw5aPYadf9DX71DNTf34C578Kledu0V2paxkVRXQhXVZlLL-uq7rCJ9j85zGjiuISDS9Thc2JBwAxLfuyRB3BZlYsuwRYll7XzWWFsmaLklEYAvvocp76KZwcfp0fTNz-tgbXhDxs3AyhVhSoQIbCaGUiFVs_TCXPNKKKMNvzUy1S60eZJAhqEAZxFdGxJ1H6G9wLnsFWWZX2BTDfaKk156kQJowzoTRqlAhkjJ7AOBKpAx8HqSUXHSlH0jozXCSdqJNe1A68R6HePkRc2pP9aUJtxJUYxEJe7TnwbpB5gouLTkxUaXHGCQ8k-ouBiGIHnnc6cDvWoEIOyDXtWPvYeg_KvCXw7mX88r_ffAv3J_PZNJl-O_qxCw84xQAok1y-gq3mcmlfI1Bq9Jt2WfwBXqUWhg |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwEB4VKlW9lNJnSh9uVantIdngJPbmiKCrbQto1YKEeolsxxEr8liRLBL8-s7kgXbpjWvsOLFm7PnGnvkG4LPMjPCV9V2E4twNx6lx9dhSArMktrrMV5qSk4-OxfQ0_HkWna2U-mqD9o2ee2VeeOX8vI2tXBRmNMSJjWZH-6ilHAcaLdJstAEPcc36YsVRb49XQiEQnPQ0jX2ajEqvPKVu0GJT5aIAd-1xQEnUKxZp45ziIf8Hm3djJleM0GQL_g6_38WeXHjLRnvm5g6z473m9xSe9NCU7XVdtuGBLZ_Bdr_4a_a1Z6j-9hwu_hQqz92iK61rGSVHdEe7rMpYfl1XdYU92MnvGaPM4hINMFOFzYkPALEtO1iiruBjViy7QFiWXtfNZYUyZ_OS0XEEtlGRnvoFnE6-n-xP3b5qg2tCHjZuhpArClQgQ2G0MpGKrR-mkmca0UWY7fqpFqn1o0wSFDUIh7iK6PqTqP0N7gkvYbOsSvsamG-01JrzVAgTxplQGjVLBDJGj2AcidSBL4PkkkVHzpG0Tg0XSSfupBe3A59QsLediFN7uneY0DPiTAxiIa92Hfg4yD3BRUY3J6q0OOOEBxL9xkBEsQOvOj24HWtQIwfkmoasfWy9BeXeEnn3cn5z7zc_wKPZwSQ5_HH8awceczoKoIBy-RY2m8ulfYd4qdHv25XxD_3bGQY |
| 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=Small-molecule+activation+of+lysosomal+TRP+channels+ameliorates+Duchenne+muscular+dystrophy+in+mouse+models&rft.jtitle=Science+advances&rft.au=Yu%2C+Lu&rft.au=Zhang%2C+Xiaoli&rft.au=Yang%2C+Yexin&rft.au=Li%2C+Dan&rft.date=2020-02-07&rft.pub=American+Association+for+the+Advancement+of+Science+%28AAAS%29&rft.issn=2375-2548&rft.eissn=2375-2548&rft.volume=6&rft.issue=6&rft_id=info:doi/10.1126%2Fsciadv.aaz2736&rft.externalDBID=HAS_PDF_LINK&rft.externalDocID=oai_HAL_hal_02493967v1 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2375-2548&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2375-2548&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2375-2548&client=summon |