title: Targeting post-translational modifications on tau as a therapeutic strategy for Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that causes early memory impairment, followed by profound progressive cognitive decline, and eventually death. Neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of AD. NFTs are deposits of insoluble aggregates of the microtubule-binding protein tau, left behind following neuronal loss. Intracellular aggregates of tau, either in soluble or insoluble forms, are thought to disrupt cellular machinery and synaptic function and ultimately lead to neuronal death. As the ultimate pathological endpoint in AD is neuronal loss, there is significant interest in understanding the causes of tau aggregation and deposition in the brain as a potential therapeutic avenue for AD. Post-translational modifications on tau are thought to be an important regulatory mechanism that may contribute to the propensity of tau to aggregate and form NFTs. In addition to phosphorylation, numerous other post-translational modifications have been observed on tau protein. The mechanisms that cause aggregation of tau are unknown, but it is likely that post-translational modifications other than phosphorylation also regulate this process. This review will discuss several post-translational modifications of tau and their roles in modulation of tau function and aggregation in AD.
authors.affiliation: Department of Neurosymptomatics, Merck Research Laboratories, West Point, PA 19486, USA. jacob_marcus@merck.com
authors.forename: Jacob Newman
authors.initials: JN
authors.lastname: Marcus
authors.forename: Joel
authors.initials: J
authors.lastname: Schachter
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D015195:Drug Design; D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016875:tau Proteins