Abstract
«Research Center of Neurology» of Russian Academy of Medical Sciences, Moscow, Russian Federation Etiology of Parkinson’s disease (PD) is still undetermined despite long-term investigations. Monogenic forms occur predominantly in young persons and amount to about 5–10% of PD cases, while most cases of the disease are sporadic and have multifactorial nature. The key molecular mechanism of neurodegeneration in PD is the conformational change of vesicular protein α-synuclein, its self-fibrilization with formation of neurotoxic cytoplasmic aggregates and Lewy bodies/ Lewy neurites. Misfolding of α-synuclein in PD is caused by specific interaction of environmental factors, genomic factors and systemic metabolism, that all together influence on such processes as cell detoxication, mitochondrial functioning, synaptic transmission and endosomal transport. The review presents possible exogenous and endogenous triggers of pathological process in PD. Among the etiologic factors, the role of different neurotoxins, mitophagy disorders, prion-like mechanism of PD development and genetics of familial and sporadic cases of PD are discussed in detail.
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