α-Synuclein in blood and brain from familial Parkinson disease with
            <i>SNCA</i>
            locus triplication

Miller, David W.; Hague, Stephen; Clarimón, Jordi; Baptista, Melisa J.; Gwinn‐Hardy, Katrina; Cookson, Mark; Singleton, Andrew B.

doi:10.1212/01.wnl.0000127517.33208.f4

Cited by 330 publications

(238 citation statements)

References 9 publications

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“…How alpha synuclein reaches serum from the brain in unknown, but blood levels of alpha synuclein may reflect the gene dosage and/or altered protein expression, since triplication of the alpha synuclein gene causes increased brain expression and a doubling of blood alpha synuclein (Miller et al, 2004). Cocaine abuse leads to state dependent increases in the levels of alpha synuclein in postmortem brain (Mash et al, 2003;Qin et al, 2005) and peripheral blood as shown in this report.…”

Section: Discussionmentioning

confidence: 52%

Alpha synuclein protein levels are increased in serum from recently abstinent cocaine abusers

Mash

Adi

Duque

et al. 2008

Drug and Alcohol Dependence

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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 thirty 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.

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Section: Discussionmentioning

confidence: 52%

Alpha synuclein protein levels are increased in serum from recently abstinent cocaine abusers

Mash

Adi

Duque

et al. 2008

Drug and Alcohol Dependence

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“…The size of the triplication region was over 2.0Mb. The expression values of messenger RNA and protein in peripheral blood and brain were twice the amount that is present in control subjects as predicted (Miller et al, 2004). Apart from the Iowan family, a www.intechopen.com Swedish-American family was also reported as a SNCA triplication family and the patients had DLB-type prognosis and pathological findings.…”

Section: Snca Triplication and Duplication In Hereditary Pdmentioning

confidence: 78%

SNCA Gene Multiplication: A Model Mechanism of Parkinson Disease

Nishioka¹,

Ross²

2011

Gene Duplication

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“…Following this initial finding, Millter, et al found that the blood level of α-synuclein monomers was doubled in familial PD patients with α-synuclein gene locus triplication [8].…”

Section: The Finding Of Extracellular α-Synuleinmentioning

confidence: 90%

The Extracellular α-Synuclein and its Biological Significance

Guo¹,

Zhen²

2013

Biochem & Pharmacol

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Abstractα-synuclein plays an important role in the development of Parkinson's disease (PD). It was believed that α-synuclein elicits its effects in the neuronal cytosol. However, the finding of extracellular α-synuclein expands the orthodox spectrum. The α-synuclein can be secreted via the multi-vesicle bodies-mediated exosome and the recycling-endosome pathway. In the intercellular milieu, the secreted α-synuclein is degraded by enzymes or engulfed by neighboring cells. The remaining α-synuclein can induce the neurotoxicity, activate microglia, and promote the pathogenesis of Parkinson's disease. In the review, we focus on the recent findings of extracellular α-synuclein and its biological significance.

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α-Synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication

Cited by 330 publications

References 9 publications

Alpha synuclein protein levels are increased in serum from recently abstinent cocaine abusers

Alpha synuclein protein levels are increased in serum from recently abstinent cocaine abusers

SNCA Gene Multiplication: A Model Mechanism of Parkinson Disease

The Extracellular α-Synuclein and its Biological Significance

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