title: Tau phosphorylation in Alzheimer's disease: pathogen or protector?
abstract: During the past decade, hypotheses concerning the pathogenesis of most neurodegenerative diseases have been dominated by the notion that the aggregation of specific proteins and subsequent formation of cytoplasmic and extracellular lesions represent a harbinger of neuronal dysfunction and death. As such, in Alzheimer's disease, phosphorylated tau protein, the major component of neurofibrillary tangles, is considered a central mediator of disease pathogenesis. We challenge this classic notion by proposing that tau phosphorylation represents a compensatory response mounted by neurons against oxidative stress and serves a protective function. This novel concept, which can also be applied to protein aggregates in other neurodegenerative diseases, opens a new window of knowledge with broad implications for both the understanding of mechanisms underlying disease pathophysiology and the design of new therapeutic strategies.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106 USA.
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Lee
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Garrett
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D008870:Microtubules / Q000502:physiology; D016874:Neurofibrillary Tangles / Q000473:pathology; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins