Genetic and environmental factors in the cause of Parkinson's disease
ABSTRACT Despite being the subject of intense study, the pathogenesis of Parkinson's disease still remains unclear. In recent years, however, there has been increasing evidence to support a role for genetic factors in its cause. This has come from twin and family studies, the mapping and cloning of PARK genes that are associated with the development of PD, and analysis of potential susceptibility genes. There is also evidence indicating that environmental factors may play a role in the disease process. It is likely that for most cases, there is a complex interplay between these genetic and environmental influences in the causation of Parkinson's disease. This article reviews the evidence in support of genetic and environmental factors in the cause of PD.
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ABSTRACT: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. It is now clear that genetic susceptibility and environmental factors play a role in disease etiology and progression. Because environmental factors are involved with the majority of the cases of PD, it is important to understand the role nutrition plays in both neuroprotection and neurodegeneration. Recent epidemiological studies have revealed the promise of some nutrients in reducing the risk of PD. In contrast, other nutrients may be involved with the etiology of neurodegeneration or exacerbate disease progression. This review summarizes the studies that have addressed these issues and describes in detail the nutrients and their putative mechanisms of action in PD.Frontiers in Aging Neuroscience 03/2014; 6:36. DOI:10.3389/fnagi.2014.00036 · 2.84 Impact Factor
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ABSTRACT: During the past three decades, the Wingless-type MMTV integration site (Wnt) signaling cascade has emerged as an essential system regulating multiple processes in developing and adult brain. Accumulating evidence points to a dysregulation of Wnt signaling in major neurodegenerative pathologies including Parkinson's disease (PD), a common neurodegenerative disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons and deregulated activation of astrocyte and microglial. This review highlights the emerging link between Wnt signaling and key inflammatory pathways during mDA neuron damage/repair in PD progression. In particular, we summarize recent evidence documenting that aging and neurotoxicant exposure strongly antagonize Wnt/¦Â-catenin signaling in mDA neurons and subventricular zone (SVZ) neuroprogenitors via astrocyte-microglial interactions. Dysregulation of the crosstalk between Wnt/¦Â-catenin signaling and anti-oxidant/anti-inflammatory pathways delineate novel mechanisms driving the decline of SVZ plasticity with age and the limited nigrostrial dopaminergic self-repair in PD. These findings hold a promise in developing therapies that target Wnt/¦Â-catenin signaling to enhance endogenous restoration and neuronal outcome in age-dependent diseases, such as PD.Journal of Molecular Cell Biology 01/2014; DOI:10.1093/jmcb/mjt053 · 8.43 Impact Factor
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ABSTRACT: Most chronic neurodegenerative diseases such as Parkinson's disease (PD) are accompanied by neuroinflammation which is associated with glial cells activation and production of different inflammatory cytokines. In the present study we evaluated the anti-cataleptic effect of silymarin pre-treatment in 6-hydroxydopamine (6-OHDA)-lesioned rats, striatum myeloperoxidase (MPO) activity and cerebrospinal fluid (CSF) levels of inflammatory cytokines. Male Wistar rats were pre-treated with intraperitonel (i.p.) injections of Silymarin (100, 200 and 300mg/kg) for 5 consecutive days. Then, catalepsy was induced by unilateral infusion of 6-OHDA (8μg/2μl/rat) into the central region of the SNc. The anti-cataleptic effect of Silymarin was assessed by the bar test 3-weeks after neurotoxin injection. Striatal myeloperoxidase activity and CSF levels of TNF-α and IL-6 were assessed at the end of behavioral experiments. Our data demonstrated that silymarin pre-treatment decreased catalepsy. The most anti-catelptic effect was observed at the dose of 300mg/kg of silymarin (p<0.001). There was a significant (p<0.001) increase in MPO activity of 6-OHDA-lesioned rats whereas; in silymarin (in all 3 doses, i.p. for 5 days) pre-treated hemi-parkinsonian rats MPO activity was decreased markedly (p<0.001). Furthermore the CSF levels of TNF-α and IL-6 were decreased (p<0.001) in silymarin (100, 200 and 300mg/kg) pre-treated rats up to the range of normal non-parkinsonian animals. From these results, it may be concluded that pre-treatment with silymarin attenuates 6-OHDA-induced catalepsy by decreasing striatal MPO activity and restores CSF concentration of inflammatory cytokines, TNF-α and IL-6 to the levels of normal non-parkinsonian rats.Neuroscience Letters 09/2013; DOI:10.1016/j.neulet.2013.09.022 · 2.06 Impact Factor