beta-Amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria.
FEBS Lett
; 457(1): 131-4, 1999 Aug 20.
Article
in En
| MEDLINE
| ID: mdl-10486579
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
Electron Transport Complex IV
/
Mitochondria
Limits:
Animals
Language:
En
Journal:
FEBS Lett
Year:
1999
Document type:
Article
Affiliation country:
United kingdom