Mitochondria and Alzheimer's disease: amyloid-beta peptide uptake and degradation by the presequence protease, hPreP.
Several lines of evidence suggest mitochondrial dysfunction as a possible underlying mechanism of Alzheimer's disease (AD). Accumulation of the amyloid-beta peptide (Abeta), a neurotoxic peptide implicated in the pathogenesis of AD, has been detected in brain mitochondria of AD patients and AD transgenic mouse models. In vitro evidence suggests that the Abeta causes mitochondrial dysfunction e.g. oxidative stress, mitochondrial fragmentation and decreased activity of cytochrome c oxidase and TCA cycle enzymes. Here we review the link between mitochondrial dysfunctions and AD. In particular we focus on the mechanism for Abeta uptake by mitochondria and on the recently identified Abeta degrading protease in human brain mitochondria.
Alikhani
Nyosha
N
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Ankarcrona
Maria
M
Glaser
Elzbieta
E
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008959:Models, Neurological; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D024101:Mitochondrial Proteins; C514899:PREP protein, human; D012697:Serine Endopeptidases