Neurodegenerative Disorders: The Role of Genetic Factors in Their Origin and the Efficiency of Treatment

The review considers the main molecular physiological causes of neurodegenerative disorders. The genetic factors involved in Parkinson’s and Alzheimer’s diseases are conventionally divided into pharmacodynamic and pharmacokinetic. The former are analyzed at the levels of dopamine (DA) neurons and polymorphism of the D₁, D₂, and D₃ DA receptors. The role of polymorphisms of some proteins such as parkin (PARK1-PARK10) and α-synuclein in generation of Lewy bodies is described. The pharmacokinetic factors play a role in Parkinson’s disease (PD) at the level of metabolism of DA, dioxyphenylalanine, and tyrosine and include polymorphisms of enzymes and proteins involved in the relevant metabolic reactions. The profile of DA metabolites may contribute to neurotoxicity and the development of PD. Prospects of drug therapy of PD and the risk of adverse drug effects such as mental disorders and dyskinesia are considered in terms of polymorphisms of enzymes and transport proteins.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 4, 2005, pp. 119–130.Original Russian Text Copyright © 2005 by Sukhanov, Ionov, Piruzyan.