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Article type: Research Article
Authors: Sinha, Maitrayee | Behera, Prajna | Bhowmick, Pritha | Banerjee, Kalpita | Basu, Sumitran | Chakrabarti, Sasanka; *
Affiliations: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, Kolkata, India
Correspondence: [*] Correspondence to: Prof. Sasanka Chakrabarti, Department of Biochemistry, Institute of Post Graduate Medical Education & Research, 244 A J C Bose Road, Kolkata, India. Tel.: +91 3322234413 and +91 9874489805; E-mail: profschakrabarti95@gmail.com; s_chakrabarti54@yahoo.co.in.
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.
Keywords: Alzheimer's disease, amyloid-β peptide, brain aging, cytochrome c, mitochondria, respiratory chain complexes
DOI: 10.3233/JAD-2011-110686
Journal: Journal of Alzheimer's Disease, vol. 27, no. 4, pp. 753-765, 2011
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