Mitochondrial membrane permeabilisation by amyloid aggregates and protection by polyphenols.

摘要: Alzheimer's disease and Parkinson's are neurodegenerative disorders characterised by the misfolding of proteins into soluble prefibrillar aggregates. These aggregate complexes disrupt mitochondrial function, initiating a pathophysiological cascade leading to synaptic neuronal degeneration. In order explore interaction amyloid aggregates with membranes, we made use two in vitro model systems, namely: (i) lipid vesicles defined membrane compositions that mimic those (ii) respiring mitochondria isolated from SH-SY5Y cells. External application forms, but not monomers, amyloid-beta (Aβ42 peptide), wild-type α-synuclein (α-syn), mutant α-syn (A30P A53T) tau-441 induced robust permeabilisation mitochondrial-like vesicles, triggered cytochrome c release (CCR) organelles. Importantly, effect on was shown be dependent upon cardiolipin, an anionic phospholipid unique well-known key player apoptosis. Pharmacological modulators ion channels failed inhibit CCR. Thus, propose generic mechanism thrilling which have intrinsic capacity permeabilise without need any other protein. Finally, six small-molecule compounds black tea extract were tested for their ability permeation membranes Aβ42, tau complexes. We found rosmarinic acid most potent mito-protectants, may thus represent important drug leads alleviate dysfunction diseases.