Mechanisms of Gene Regulation in Alcoholism: Role of α-Synuclein in the Pathophysiology of Alcohol Misuse

Abstract

The pathophysiology of alcohol addiction is still unknown. Current research is focusing on understanding the mechanisms involved in the neurotoxic effects of ethanol on the brain and the genetic risk factors associated with alcohol misuse. The prefrontal cortex is particularly susceptible to neurotoxic damage, and neuronal loss in this region has been associated with long-term alcohol misuse. As the prefrontal cortex is involved in the development and persistence of alcohol addiction, ethanol induced neurotoxic damage in this region is likely to amplify the reinforcing effects of alcohol. α-Synuclein (SNCA), a protein abundantly expressed in neurons and involved in the dopaminergic reward pathway, has a well-established role in neurodegenerative and neuropsychological disorders, and is a candidate gene for alcohol misuse. Changes to α- synuclein expression may therefore have severe consequences on these key pathways and may increase susceptibility to alcohol addiction. This thesis investigated the regulation of α-synuclein expression and its potential role in the pathophysiology of chronic alcohol misuse.