Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies

• Published in: Science (American Association for the Advancement of Science) Vol. 371; no. 6532
• Main Authors: Chang, Che-Wei, Shao, Eric, Mucke, Lennart
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 26.02.2021
• Subjects: 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
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abb8255

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.