Does alpha-synuclein confer protection or damage to dopaminergic neurons in Parkinson's disease?
Alpha-synuclein is a principal component of Lewy bodies and Lewy neurites, which are pathologic hall-marks of Parkinson's disease.
Alpha-synuclein is generally considered to play a role in synaptic activity, although its function remains largely unknown.
Accumulative evidence has been shown that aggregated extracellular alpha-synuclein fibrils can be internalized in the cells and enhance the intracellular formation of protein inclusions, leading to cell death. Conversely, there is emerging evidence suggesting that alpha-synuclein has also neuroprotective effects.
In one study, extracellular alpha-synuclein treatment at nanomolar concentrations protected neurons against cellular stresses such as serum deprivation, oxidative stress, and excitotoxicity through the PI3/Akt signaling pathway.
In a transgenic mouse model, the increased expression of alpha-synuclein prevented paraquat-induced dopaminergic cell degeneration.
Thus far, it is uncertain as to whether alpha-synuclein plays a favorable role for neurons at nanomolar concentrations.
Beom S. Jeon and team from Inje University Seoul Paik Hospital in South Korea for the first time provide evidence that extracellular alpha-synuclein enhances neuronal survival at a nanomolar concentration (50 and 100 nmol/L) and this effect is most likely mediated by the Akt pathway. Their study published in Neural Regeneration Research (Vol. 8, No. 35, 2013) can update the role of alpha-synuclein in neuronal cells and its involvement in Parkinson's disease and related diseases.