Protein misfolding in alzheimer’s disease: Pathogenic or protective?

Rudy J. Castellani, Hyoung Gon Lee, Akihiko Nunomura, Xiongwei Zhu, George Perry, Mark A. Smith

Research output: Chapter in Book/Report/Conference proceedingChapter


For nearly a century, the pathological hallmarks of Alzheimer’s disease (AD), namely senile plaques and neuro?brillary tangles (NFT), have been suspected to play a major role in disease pathogenesis. This, not surprisingly, has led the ?eld to focus on the biochemistry of amyloid-b deposition as senile plaques, or the phosphorylation and aggregation of tau as NFT. In this review we take a contrary view, where, rather than remaining initiators of disease pathogenesis, we suspect that the lesions function as a primary line of antioxidant defense. If amyloid-b and tau accumulations re?ect a physiological reaction to chronic stress, the rationale of current therapeutic efforts targeted toward lesion removal would obviously be misguided. Expanding beyond AD, we suspect that this concept of protection is also true for misfolded proteins and pathological lesions in other neurodegenerative diseases.

Original languageEnglish (US)
Title of host publicationProtein Misfolding in Neurodegenerative Diseases
Subtitle of host publicationMechanisms and Therapeutic Strategies
PublisherCRC Press
Number of pages10
ISBN (Electronic)9781420007145
ISBN (Print)9780849373107
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • General Chemistry
  • General Medicine
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience


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