Beta-amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria

Canevari, Laura and Clark, John B. and Bates, Timothy E. (1999) Beta-amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria. FEBS Letters, 457 (1). pp. 131-4. ISSN 0014-5793

Full content URL: http://dx.doi.org/10.1016/S0014-5793(99)01028-5

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Item Type:Article
Item Status:Live Archive

Abstract

Defects in mitochondrial oxidative metabolism, in particular decreased activity of cytochrome c oxidase, have been demonstrated in Alzheimer's disease, and after the expression of the amyloid precursor protein (APP) in cultured cells, suggesting that mitochondria might be involved in beta-amyloid toxicity. Recent evidence suggests that the proteolysis of APP to generate beta-amyloid is at least in part intracellular, preceding the deposition of extracellular fibrils. We have therefore investigated the effect of incubation of isolated rat brain mitochondria with the beta-amyloid fragment 25-35 (100 microM) on the activities of the mitochondrial respiratory chain complexes I, II-III, IV (cytochrome c oxidase) and citrate synthase. The peptide caused a rapid, dose-dependent decrease in the activity of complex IV, white it had no effect on the activities on any of the other enzymes tested. The reverse sequence peptide (35-25) had no effect on any of the activities measured. We conclude that inhibition of mitochondrial complex IV might be a contributing factor to the pathogenesis of Alzheimer's disease.

Keywords:amyloid precursor protein, amyloid, Mitochondria, brain
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B140 Neuroscience
A Medicine and Dentistry > A300 Clinical Medicine
B Subjects allied to Medicine > B130 Pathology
Divisions:College of Science > School of Life Sciences
ID Code:5293
Deposited On:09 Jun 2013 18:08

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