The number of the people affected by neurodegenerative disorders is growing dramatically due to the ageing of population. The major neurodegenerative diseases share some common pathological features including the involvement of mitochondria in the mechanism of pathology and misfolding and the accumulation of abnormally aggregated proteins. Neurotoxicity of aggregated β-amyloid, tau, α-synuclein and huntingtin is linked to the effects of these proteins on mitochondria. All these misfolded aggregates affect mitochondrial energy metabolism by inhibiting diverse mitochondrial complexes and limit ATP availability in neurones. β-Amyloid, tau, α-synuclein and huntingtin are shown to be involved in increased production of reactive oxygen species, which can be generated in mitochondria or can target this organelle. Most of these aggregated proteins are capable of deregulating mitochondrial calcium handling that, in combination with oxidative stress, lead to opening of the mitochondrial permeability transition pore. Despite some of the common features, aggregated β-amyloid, tau, α-synuclein and huntingtin have diverse targets in mitochondria that can partially explain neurotoxic effect of these proteins in different brain regions.
Interaction of misfolded proteins and mitochondria in neurodegenerative disorders
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Andrey Y. Abramov, Alexey V. Berezhnov, Evgeniya I. Fedotova, Valery P. Zinchenko, Ludmila P. Dolgacheva; Interaction of misfolded proteins and mitochondria in neurodegenerative disorders. Biochem Soc Trans 15 August 2017; 45 (4): 1025–1033. doi: https://doi.org/10.1042/BST20170024
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