Mitochondrial dysfunction and Alzheimer's disease

Role of amyloid-β peptide alcohol dehydrogenase (ABAD)

Shi Du Yan, David Stern

Research output: Contribution to journalReview article

89 Citations (Scopus)

Abstract

An important means of determining how amyloid-beta peptide (Aβ) affects cells is to identify specific macromolecular targets and assess how Aβ interaction with such targets impacts on cellular functions. On the one hand, cell surface receptors interacting with extracellular Aβ have been identified, and their engagement by amyloid peptide can trigger intracellular signaling cascades. Recent evidence has indicated a potentially significant role for deposition of intracellular Aβ in cell stress associated with amyloidosis. Thus, specific intracellular targets of Aβ might also be of interest. Our review evaluates the potential significance of Aβ interaction with a mitochondrial enzyme termed Aβ-binding alcohol dehydrogenase (ABAD), a member of the short-chain dehydrogenase-reductase family concentrated in mitochondria of neurones. Binding of Aβ to ABAD distorts the enzyme's structure, rendering it inactive with respect to its metabolic properties, and promotes mitochondrial generation of free radicals. Double transgenic mice in which increased levels of ABAD are expressed in an Aβ-rich environment, the latter provided by a mutant amyloid precursor protein transgene, demonstrate accelerated decline in spatial learning/memory and pathologic changes. These data suggest that mitochondria ABAD, ordinarily a contributor to metabolic homeostasis, has the capacity to become a pathogenic factor in an Aβ-rich environment.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalInternational Journal of Experimental Pathology
Volume86
Issue number3
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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Mitochondrial Diseases
Alcohol Dehydrogenase
Amyloid
Alzheimer Disease
Peptides
Mitochondria
Amyloid beta-Peptides
Cell Surface Receptors
Amyloidosis
Mutant Proteins
Enzymes
Transgenes
Transgenic Mice
Free Radicals
Oxidoreductases
Homeostasis
Neurons

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Mitochondrial dysfunction and Alzheimer's disease : Role of amyloid-β peptide alcohol dehydrogenase (ABAD). / Yan, Shi Du; Stern, David.

In: International Journal of Experimental Pathology, Vol. 86, No. 3, 01.06.2005, p. 161-171.

Research output: Contribution to journalReview article

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