TY - JOUR
T1 - Tau phosphorylation in Alzheimer's disease
T2 - Pathogen or protector?
AU - Lee, Hyoung Gon
AU - Perry, George
AU - Moreira, Paula I.
AU - Garrett, Matthew R.
AU - Liu, Quan
AU - Zhu, Xiongwei
AU - Takeda, Atsushi
AU - Nunomura, Akihiko
AU - Smith, Mark A.
N1 - Funding Information:
Work in the authors' laboratories is supported in part the Alzheimer's Association, John Douglas French Alzheimer's Foundation, Philip Morris USA Inc. and Philip Morris International.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molmed.2005.02.008
DO - 10.1016/j.molmed.2005.02.008
M3 - Article
C2 - 15823754
AN - SCOPUS:17044435830
VL - 11
SP - 164
EP - 169
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
SN - 1471-4914
IS - 4
ER -