title: The Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy.
abstract: Microtubule-associated protein tau (MAPT) is a gene responsible for encoding tau protein, which is tightly implicated in keeping the function of microtubules and axonal transport. Hyperphosphorylated tau protein participates in the formation of neurofibrillary tangles (NFTs), which characterize many neurodegenerative disorders termed tauopathies. Genome-wide association studies (GWAS) have demonstrated numerous single nucleotide polymorphisms (SNPs) located in MAPT associated with various neurodegenerative diseases. Thus, it has been presumed that MAPT plays a crucial role in pathogenesis of neurodegeneration via affecting the structure and function of tau. Here, we review the advanced studies to summarize the biochemical properties of MAPT and its encoded protein, as well as the genetics and epigenetics of MAPT in neurodegeneration. Finally, given the potential mechanisms of MAPT to neurodegeneration pathogenesis, targeting MAPT and tau might present significant treatments of MAPT mutation-related neurodegeneration. Affirmatively, the identification of MAPT is extremely beneficial for improving our understanding of the pathogenesis of various neurodegenerative diseases and developing the mechanism-based therapies.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Xing
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China. dr.tanlan@163.com.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. yu-jintai@163.com.|Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA. yu-jintai@163.com.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods / Q000639:trends*; D055106:Genome-Wide Association Study / Q000379:methods / Q000639:trends*; D006801:Humans; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D024801:Tauopathies / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D016875:tau Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Genetics; MAPT; Neurodegeneration; Pathogenesis; Therapy