Tau phosphorylation in Alzheimer's disease: Pathogen or protector?

Hyoung Gon Lee, George Perry, Paula I. Moreira, Matthew R. Garrett, Quan Liu, Xiongwei Zhu, Atsushi Takeda, Akihiko Nunomura, Mark A. Smith

Research output: Contribution to journalArticlepeer-review

212 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)164-169
Number of pages6
JournalTrends in Molecular Medicine
Issue number4
Publication statusPublished - 2005 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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