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Alpha-Synuclein Toxicity on Protein Quality Control, Mitochondria and Endoplasmic Reticulum

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Abstract

Parkinson’s disease (PD) is characterized by the presence of insoluble protein clusters containing α-synuclein. Impairment of mitochondria, endoplasmic reticulum, autophagy and intracellular trafficking proper function has been suggested to be caused by α-synuclein toxicity, which is also associated with the higher levels of ROS found in the aged brain and in PD. Oxidative stress leads to protein oligomerization and aggregation that impair autophagy and mitochondrial dynamics leading to a vicious cycle of organelles damage and neurodegeneration. In this review we focused on the role of α-synuclein dysfunction as a cellular stressor that impairs mitochondria, endoplasmic reticulum, autophagy and cellular dynamics culminating with dopaminergic depletion and the pathogenesis of PD.

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Acknowledgements

MFRF is supported by research grants from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) (2011/06434-7; 2013/08028-1; 2015/18961-2), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq).

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  1. Departamento de Genética e Biologia Evolutiva, Instituto de Biociencias, Universidade de Sao Paulo, Rua do Matao, 277, Cidade Universitaria, 05508-090, Sao Paulo, SP, Brazil

    Thaiany Quevedo Melo & Merari F. R. Ferrari

  2. Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Thaiany Quevedo Melo & Sjef J. C. V. M. Copray

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Melo, T.Q., Copray, S.J.C.V.M. & Ferrari, M.F.R. Alpha-Synuclein Toxicity on Protein Quality Control, Mitochondria and Endoplasmic Reticulum. Neurochem Res 43, 2212–2223 (2018). https://doi.org/10.1007/s11064-018-2673-x

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