Interaction between Neuromelanin and Alpha-Synuclein in Parkinson's Disease

• Published in: Biomolecules (Basel, Switzerland) Vol. 5; no. 2; pp. 1122 - 1142
• Main Authors: Xu, Shengli, Chan, Piu
• Format: Journal Article Book Review
• Language: English
• Published: Switzerland MDPI AG 05.06.2015; MDPI
• Subjects: alpha-synuclein; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Animals; Humans; Melanins - metabolism; neuromelanin; Oxidative Stress; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Protein Aggregation, Pathological - metabolism; Review; alpha-synuclein; Parkinson’s disease; oxidative stress; neuromelanin
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom5021122

Parkinson's disease (PD) is a very common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) into Lewy body (LB) inclusions and the loss of neuronmelanin (NM) containing dopamine (DA) neurons in the substantia nigra (SN). Pathological α-syn and NM are two prominent hallmarks in this selective and progressive neurodegenerative disease. Pathological α-syn can induce dopaminergic neuron death by various mechanisms, such as inducing oxidative stress and inhibiting protein degradation systems. Therefore, to explore the factors that trigger α-syn to convert from a non-toxic protein to toxic one is a pivotal question to clarify the mechanisms of PD pathogenesis. Many triggers for pathological α-syn aggregation have been identified, including missense mutations in the α-syn gene, higher concentration, and posttranslational modifications of α-Syn. Recently, the role of NM in inducing α-syn expression and aggregation has been suggested as a mechanism for this pigment to modulate neuronal vulnerability in PD. NM may be responsible for PD and age-associated increase and aggregation in α-syn. Here, we reviewed our previous study and other recent findings in the area of interaction between NM and α-syn.