The heat shock/oxidative stress connection: Relevance to Alzheimer disease

M. A. Pappolla, M. Sos, R. A. Omar, K. Sambamurti

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Involvement of free-radical oxidations in the aging process has been a topic of interest since Harman's original contribution. Because of the close association between aging and Alzheimer disease (AD) and the qualitative similarity in the neuropathology of both conditions, it has been proposed by many investigators that oxidative stress may be important in AD. If such modality of injury was indeed involved, one should expect to find markers of oxidation and heat shock (since free radicals are key mediators of heat- shock induction) in brains of patients with AD. In fact, several studies documented abnormal expression of antioxidant enzymes and heat-shock proteins (HSP) along with other markers of oxidation in AD brains. We showed that abnormally expressed antioxidant enzymes are topographically associated with senile plaques and neurofibrillary tangles, and that the activity of these enzymes is (contrary to what one would expect) markedly reduced. These findings have recently been confirmed by other investigators. Despite a large amount of evidence that suggests an association between oxidative stress and the pathogenesis of AD, it is not yet known whether oxidative stress is a cause or consequence of the disorder. Future research efforts regarding the oxidative stress hypothesis of AD should include attempts at generating AD pathology by oxidative means in laboratory animals, determining the role and integrity of the heat-shock response in AD, as well as that of various antioxidant systems, growth factors, and hormones with antioxidant and neuroprotective properties.

Original languageEnglish (US)
Pages (from-to)21-34
Number of pages14
JournalMolecular and Chemical Neuropathology
Issue number1-3
StatePublished - 1996
Externally publishedYes


  • Alzheimer disease
  • Free-radical oxidations
  • aging
  • antioxidant enzymes
  • heat shock
  • heat-shock proteins
  • neurofibrillary tangles
  • oxidative stress
  • senile plaques

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology


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