Modulation of alpha-synuclein aggregation by dopamine: a review.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by (1) the selective loss of dopaminergic neurons in the substantia nigra and (2) the deposition of misfolded alpha-synuclein (alpha-syn) as amyloid fibrils in the intracellular Lewy bodies in various region of the brain. Current thinking suggests that an interaction between alpha-syn and dopamine (DA) leads to the selective death of neuronal cells and the accumulation of misfolded alpha-syn. However, the exact mechanism by which this occurs is not fully defined. DA oxidation could play a key role is the pathogenesis of PD by causing oxidative stress, mitochondria dysfunction and impairment of protein metabolism. Here, we review the literature on the role of DA and its oxidative intermediates in modulating the aggregation pathways of alpha-syn.
Leong
Su Ling
SL
Department of Pathology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
Cappai
Roberto
R
Barnham
Kevin Jeffrey
KJ
Pham
Chi Le Lan
CL
D000818:Animals; D016923:Cell Death / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D017510:Protein Folding; D051844:alpha-Synuclein / Q000378:metabolism / Q000502:physiology*
D051844:alpha-Synuclein; D004298:Dopamine