Modern views on etiology and pathogenesis of Parkinson's disease

Aim. To analyze the specialized scientific literature for data generalization concerning current views on etiology and pathogenesis of Parkinson's disease (PD). PD is a chronic progressive CNS disease, mainly associated with degeneration of brain's dopamine-producing neurons, motor and nonmotor violations and resulting in persistent disability. Although the PD is the most studied disease among all parkinsonism disorders, there is no consensus on its nature until now. The basis of PD pathomorphology and neurological degeneration is a violation of a-synuclein protein with Lewy's bodies accumulation in the cells. The formation of pathological a-synuclein is connected with features of genotype, environmental agents and internal processes in the body. The review presents the current data about etiological and pathogenic mechanisms of PD development. Special attention is paid to the role of genetics, the influence of exogenous agents and the basic factors in the pathogenesis of the disease. Conclusions. A number of questions of PD etiology and pathogenesis are not quite certain for today. Pathogenetic mechanism of degeneration in PD is heterogeneous: mitochondrial dysfunction, oxidative stress, of proteolytic functions violations (ubiquitin-proteasome system). The reasons which start the degenerative process are varied, and can be both external and internal, as well as their interaction also is possible, which determines the probability of PD development. Sporadic forms of PD pathogenesis are noticeably different from disease with hereditary predisposition. Verification of risk factors if genes predisposing to the disease development are present has a key role for the complex preventive measures formation in patients with a predisposition to the disease. Despite the fact that genetics has the primary importance in the process initiation for persons with a family history, varied clinical scenario of PD with the presence of identical genetic mutations demonstrates the importance of external factors and their populational specificity. Their identification will provide the basis for the effective preventive and predictive capabilities development. Further study of the role of inflammation, excitotoxicity and oxidative stress in the PD pathogenesis could probably provide an opportunity to change symptomatic therapy of the disease into pathogenetic in the future.