Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease

Moore, Robert Y.

doi:10.1016/s1353-8020(03)00063-4

Cited by 39 publications

(17 citation statements)

References 42 publications

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“…Although both the prefrontal cortex and the striatum receive dopaminergic innervation, the striatum receives a far denser projection and the input is from the substantia nigra pars compacta, which undergoes selective and extensive neurodegeneration in PD (Moore, 2003;Seamans and Yang, 2004). In addition, evidence suggests that dopaminergic neurodegeneration may begin with loss of striatal nerve terminals and a 'dying back' process (Dauer and Przedborski, 2003).…”

Section: Discussionmentioning

confidence: 99%

Selective enrichment of DJ‐1 protein in primate striatal neuronal processes: Implications for Parkinson's disease

Olzmann

Bordelon

Muly

et al. 2006

J of Comparative Neurology

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Mutations in DJ-1 cause autosomal recessive, early-onset Parkinson's disease (PD). The precise function and distribution of DJ-1 in the central nervous system remain unclear. In this study, we performed a comprehensive analysis of DJ-1 expression in human, monkey, and rat brains using antibodies that recognize distinct, evolutionarily conserved epitopes of DJ-1. We found that DJ-1 displays region-specific neuronal and glial labeling in human and non-human primate brain, sharply contrasting the primarily neuronal expression pattern observed throughout rat brain. Further immunohistochemical analysis of DJ-1 expression in human and non-human primate brains showed that DJ-1 protein is expressed in neurons within the substantia nigra pars compacta and striatum, two regions critically involved in PD pathogenesis. Moreover, immunoelectron microscopic analysis revealed a selective enrichment of DJ-1 within primate striatal axons, presynaptic terminals, and dendritic spines with respect to the DJ-1 expression in prefrontal cortex. Together, these findings indicate neuronal and synaptic expression of DJ-1 in primate subcortical brain regions and suggest a physiological role for DJ-1 in the survival and/or function of nigral-striatal neurons. KeywordsPARK7; substantia nigra; striatum; electron microscopy; primate brain; distribution Parkinson's disease (PD) is a debilitating neurodegenerative movement disorder characterized by the relatively selective degeneration of nigral dopaminergic neurons (Lang and Lozano, 1998a;Lang and Lozano, 1998b). Recently, mutations in the gene encoding DJ-1 have been identified as the genetic defect responsible for the PARK7-associated autosomal recessive, early-onset form of familial PD (Abou-Sleiman et al., 2004;Bonifati et al., 2003). Accumulating evidence suggests that loss of DJ-1 function results in neurodegeneration, but the exact role of DJ-1 in the pathogenesis of PD is unknown (Cookson, 2005;Moore et al., 2005). Using X-ray crystallography, we and others have shown that DJ-1 is a 189 amino acid protein that adopts a helix-strand-helix dimeric structure with homology to the bacterial NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript protease PH1704 and Escherichia coli chaperone protein Hsp31 (Huai et al., 2003;Lee et al., 2003;Tao and Tong, 2003). Although the precise physiological function of DJ-1 remains unclear, DJ-1 has been implicated in several cellular processes including regulation of transcription, protein quality control, and oxidative stress response (Bonifati et al., 2004;Cookson, 2005;Moore et al., 2005). In addition, targeted disruption of DJ-1 gene expression in mice leads to altered dopamine D2 receptor signaling (Chen et al., 2005;Goldberg et al., 2005) and increased susceptibility to MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine)-induced neurodegeneration (Kim et al., 2005).The distribution of DJ-1 protein is controversial and remains poorly characterized. We previously showed that DJ-1 is mainly neuronal in cortical and subcor...

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Section: Discussionmentioning

confidence: 99%

Selective enrichment of DJ‐1 protein in primate striatal neuronal processes: Implications for Parkinson's disease

Olzmann

Bordelon

Muly

et al. 2006

J of Comparative Neurology

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“…Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopamine containing neurons primarily within the substantia nigra pars compacta of the midbrain (Obeso et al, 2000;Moore, 2003). The disease is typically characterised and diagnosed by a syndrome of bradykinesia, tremor, and muscular rigidity (Stern, 1988;Gelb, Oliver & Gilman, 1999).…”

Section: Introductionmentioning

confidence: 99%

Impulse control disorders in Parkinson’s disease: Predominant role of psychological determinants

Garlovsky

Simpson

Grünewald

et al. 2016

Psychology & Health

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Objectives: Impulse Control Disorders (ICDs) in Parkinson's disease (PD) have previously almost exclusively been considered to result from anti-parkinsonian medication. However, this biomedical perspective has failed to achieve a full understanding of the phenomenon and it is argued that a failure to consider psychological factors is a critical omission. Design: The present study examined the predictive relationship between ICDs in PD and a range of

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“…137,138 A hallmark of PD is gliosis and degeneration of dopaminergic neurons in the substantia nigra are not the only features of PD. It also involves selective denervation, 139 dysfunctions in the mitochondrial and ubiquitin-proteosome system, and oxidative and nitrosative stress. 140 Available drugs for PD neither surpass nor reverse disease progression 141 and BBB causes additional challenge in drug delivery.…”

Section: Parkinson Diseasementioning

confidence: 99%

Nanomedicine in Central Nervous System (CNS) Disorders: A Present and Future Prospective

Soni¹,

Ruhela²,

Medhi³

2016

Adv Pharm Bull

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Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease

Cited by 39 publications

References 42 publications

Selective enrichment of DJ‐1 protein in primate striatal neuronal processes: Implications for Parkinson's disease

Selective enrichment of DJ‐1 protein in primate striatal neuronal processes: Implications for Parkinson's disease

Impulse control disorders in Parkinson’s disease: Predominant role of psychological determinants

Nanomedicine in Central Nervous System (CNS) Disorders: A Present and Future Prospective

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