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Xjenza Online Vol. 2 Iss. 2 - October 2014
Select polyphenols protect mitochondria against amyloid aggregates in Alzheimer and Parkinson diseases

Authors: Mario Caruana, Neville Vassallo

Corresponding: Neville Vassallo (neville.vassallo@um.edu.mt)

Keywords: Alzheimer's disease, Parkinson's disease, amyloid-beta, a-synuclein, mitochondrial membrane, permeabilisation, cardiolipin, polyphenols

Doi: http://dx.medra.org/10.7423/XJENZA.2014.2.12

Abstract:
Alzheimer and Parkinson diseases are agerelated neurodegenerative disorders in which formation of amyloid aggregates by amyloid-beta (Abeta) and a-synuclein (aS) proteins, respectively, are recognised critical events that occur early in the disease process. These aggregates cause disruption of mitochondrial function in neurons, initiating a pathophysiological cascade leading to bio-energetic collapse and ultimately neuronal cell death. The detailed mechanisms are, however, largely unknown. In vitro studies in our laboratory aimed to, (i) investigate destabilisation of mitochondrial phospholipid membranes by these amyloid aggregates and, (ii) explore the protective effect of select polyphenolic compounds on mitochondria. Exposure of mitochondria, isolated from human neuroblastoma SH-SY5Y cells, to amyloid aggregates induced a strong and dose-dependent release of cytochrome c, re ecting damage to the outer and/or inner mitochondrial membranes. Importantly, targeting of aggregates to mitochondria was shown to be dependent upon cardiolipin, a mitochondria-speci c phospholipid known to play a critical role in launching apoptosis. Moreover, the ability of amyloid aggregates to damage mitochondrial membranes was con rmed using a liposome permeabilisation assay. Finally, we found that the polyphenol compounds morin, rosmarinic acid, epigallocatechingallate and black tea extract were potent mito-protectants, and may thus delay the onset of neurodegenerative diseases.