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Alpha-synuclein and beta-amyloid different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration

Angelova, PR; Abramov, AY; (2017) Alpha-synuclein and beta-amyloid different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration. Biochemical and Biophysical Research Communications , 483 (4) pp. 1110-1115. 10.1016/j.bbrc.2016.07.103. Green open access

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Abstract

Two of the most devastating neurodegenerative diseases are consequences out of misfolding and aggregation of key proteins-alpha synuclein and beta-amyloid. Although the primary targets for the two proteins are different, they both share a common mechanism that involves formation of pore-like structure on the plasma membrane, consequent dysregulation of calcium homeostasis, mitochondrial dysfunction and oxidative damage. The combined effect of all this factors ultimately leads to neuronal cell death. Whereas beta amyloid acts on the astrocytic plasma membrane, exhibiting a tight dependence to the membrane cholesterol content, alpha–synuclein does not distinguish between type of membrane or cell. Additionally, oligomeric forms of both proteins produce reactive oxygen species through different mechanisms: beta-amyloid through activation of the NADPH oxidase and alpha-synuclein through non-enzymatic way. Finally, both peptides in oligomeric form induce mitochondrial depolarisation through calcium overload and free radical production that ultimately lead to opening of the mitochondrial permeability transition pore and trigger cell death.

Type: Article
Title: Alpha-synuclein and beta-amyloid different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbrc.2016.07.103
Publisher version: http://dx.doi.org/10.1016/j.bbrc.2016.07.103
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, PERMEABILITY TRANSITION PORE, COMPLEX I DEFICIENCY, PARKINSONS-DISEASE, ALZHEIMERS-DISEASE, OXIDATIVE STRESS, ION CHANNELS, VESICLE PERMEABILIZATION, INDUCED NEUROTOXICITY, LIPID-PEROXIDATION, PRECURSOR PROTEIN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1508935
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