alpha-synuclein and Disruptive--Impulse-Control--and-Conduct-Disorders

Lysosomal transport of cargos in neurons is essential for neuronal proteostasis, transmission and functional motors and behaviours. Lysosomal malfunction including storage disorders is involved in the pathogenesis of Parkinson's disease (PD). Given the unclear molecular mechanisms of diverse defects in PD phenotypes, especially behavioural deficits, this mini review explores the cellular contexts of PD impulse control disorders and the molecular aspects of lysosomal cross-membrane transports. Focuses are paid to trace metal involvements in α-synuclein assembly in Lewy bodies, the functions and molecular interactions of ATP13A2 as ATPase transporters in lysosomal membranes for cross-membrane trafficking and lysosomal homeostasis, and our current understandings of the neural circuits in ICD. Erroneously polarized distributions of cargos such as metals and lipids on each side of lysosomal membranes triggered by gene mutations and deregulated expression of ATP13A2 may thus instigate sensing protein structural changes such as aggregations, organelle degeneration, and specific neuronal ageing and death in Parkinsonism.

Topics: alpha-Synuclein; Animals; Disruptive, Impulse Control, and Conduct Disorders; Humans; Intracellular Membranes; Lewy Bodies; Lysosomes; Manganese; Neurons; Parkinson Disease; Protein Transport; Proton-Translocating ATPases

Topics: Adult; Alleles; alpha-Synuclein; Disruptive, Impulse Control, and Conduct Disorders; Female; Genetics, Behavioral; Genotype; Homozygote; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk; Young Adult

Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. Recent studies have shown increased alpha synuclein protein expression in serum of alcoholic patients that is linked with severity of alcohol craving. The aim of this study was to analyze the serum levels of alpha synuclein in healthy subjects and in recently abstinent cocaine abusers. Alpha synuclein protein expression was measured by enzyme-linked immunosorbent assay in serum specimens obtained from 38 recently abstinent cocaine dependent patients and 14 control subjects. The presence of cocaine dependence disorder was based on the Structured Clinical Interview (DSM-IV). Drug severity was assessed by the Addiction Severity Index ratings and composite measures. Scores of the intensity and frequency of cocaine craving episodes were obtained from the Minnesota Cocaine Craving Questionnaire. The serum concentrations of alpha synuclein in cocaine dependent patients were significantly higher as compared with age-matched drug-free controls (p<0.001). Alpha synuclein levels in blood were significantly correlated with the intensity (r=0.60, p<0.001) and frequency (r=0.64, p<0.001) of cocaine craving and with 30 days of cocaine use in the prior month before entry to treatment (r=0.56, p<0.005). However, there was no correlation between the serum protein levels of alpha synuclein and age in either group. This report is the first demonstration of altered alpha synuclein levels in peripheral blood from cocaine abusers. These data agree with previous reports in postmortem brain of cocaine abusers and provide support for an association between alpha synuclein and cocaine dependence.

Topics: Adult; alpha-Synuclein; Cocaine-Related Disorders; Disruptive, Impulse Control, and Conduct Disorders; Dopamine; Female; Humans; Interview, Psychological; Male; Mass Screening; Surveys and Questionnaires