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

• Published in: Neurochemical research Vol. 43; no. 12; pp. 2212 - 2223
• Main Authors: Melo, Thaiany Quevedo, Copray, Sjef J. C. V. M., Ferrari, Merari F. R.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-12-2018; Springer Nature B.V
• Subjects: alpha-Synuclein - genetics; alpha-Synuclein - metabolism; alpha-Synuclein - toxicity; Amino Acid Sequence; Animals; Autophagy; Autophagy - drug effects; Autophagy - physiology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Cell Biology; Disease control; Dopamine receptors; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - genetics; Endoplasmic Reticulum - metabolism; Humans; Mitochondria; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; Movement disorders; Neurochemistry; Neurodegeneration; Neurodegenerative diseases; Neurology; Neurosciences; Oligomerization; Organelles; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Pathogenesis; Phagocytosis; Protein Transport - physiology; Proteins; Quality control; Reactive oxygen species; Reactive Oxygen Species - metabolism; Review Paper; Synuclein; Toxicity; Aging; Oxidative stress; Parkinson’s disease
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-018-2673-x

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.