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

Author(s)

Melo, Thaiany Quevedo ^{[1, 2]} ; Copray, Sjef J. C. V. M. ^[2] ; Ferrari, Merari F. R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Rua Matao 277, BR-05508090 Sao Paulo, SP - Brazil

^[2] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Groningen - Netherlands

• Document type: Review article
• Source: Neurochemical Research; v. 43, n. 12, p. 2212-2223, DEC 2018.
• Web of Science Citations: 5

Abstract

Parkinson's disease (PD) is characterized by the presence of insoluble protein clusters containing -synuclein. Impairment of mitochondria, endoplasmic reticulum, autophagy and intracellular trafficking proper function has been suggested to be caused by -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 -synuclein dysfunction as a cellular stressor that impairs mitochondria, endoplasmic reticulum, autophagy and cellular dynamics culminating with dopaminergic depletion and the pathogenesis of PD. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/06434-7 - Degradation of hyperphosphorylated tau and organelles trafficking during neurodegenerative processes linked to protein aggregation in hypoccampal cell cultures
• Grantee: Merari de Fátima Ramires Ferrari
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/18961-2 - Study of autophagy as the driving mechanism of neurodegenerative diseases
• Grantee: Merari de Fátima Ramires Ferrari
• Support Opportunities: Regular Research Grants