title: Aging promotes amyloid-β peptide induced mitochondrial dysfunctions in rat brain: a molecular link between aging and Alzheimer's disease.
abstract: The entangled relationship of brain aging, mitochondrial dysfunction, and amyloid-β peptide (Aβ₄₂) toxicity occupies the center stage in the pathogenesis of Alzheimer's disease (AD). The present study examines some of the toxic effects of Aβ₄₂ on brain mitochondria and provides evidence that aged brain mitochondria are significantly more vulnerable to Aβ₄₂ toxicity. In particular, the study has shown that the aggregated, but not the monomeric, form of Aβ₄₂ in varying concentrations (10-40 μM) during in vitro incubation causes a loss of mitochondrial membrane potential, a decrease in phosphorylation capacity and ATP synthesis, and the release of cytochrome c from the mitochondria but without any noticeable change in the activities of respiratory chain complexes. Such effects of Aβ₄₂ are strikingly more conspicuous on aged rat (22-24 months) brain mitochondria compared to that on brain mitochondria of young rats (4-6 months). More interestingly is the observation that in contrast to young rat brain mitochondria, a significantly higher level of Aβ₄₂ remains associated with aged brain mitochondria under basal incubation condition as well as after exposure to exogenously added peptide. Extrapolated to an in vivo scenario, the results have clear implications in AD pathogenesis and also partly explain why brain aging is a dominant risk factor for this disease condition.
authors.affiliation: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, Kolkata, India.
authors.forename: Maitrayee
authors.initials: M
authors.lastname: Sinha
authors.forename: Prajna
authors.initials: P
authors.lastname: Behera
authors.forename: Pritha
authors.initials: P
authors.lastname: Bhowmick
authors.forename: Kalpita
authors.initials: K
authors.lastname: Banerjee
authors.forename: Sumitran
authors.initials: S
authors.lastname: Basu
authors.forename: Sasanka
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000097:blood / Q000187:drug effects*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000648:ultrastructure*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000255:Adenosine Triphosphate; D045304:Cytochromes c