Genetics of Parkinson's disease
ABSTRACT Parkinson's disease is the second most common neurodegenerative disorder and affects 2% of the population over the age of 60 years. Due to the increasing proportion of elderly individuals in developed countries, Parkinson's disease and related neurodegenerative disorders represent a growing burden on the health care system. In the majority of cases, the cause of the disease is still unknown, and its elucidation remains one of the major challenges of the neurosciences. Recent findings in rare genetic forms of Parkinson's disease have allowed the development of novel animal models, providing a basis for a better understanding of the molecular pathogenesis of the disease, setting the stage for the development of novel treatment strategies.
Several novel genes for monogenic forms of Parkinson's disease, such as PINK-1 for an autosomal-recessive early-onset variant, and LRRK2 for a relatively common late-onset autosomal-dominant form have recently been discovered, and several novel animal models have been generated on the basis of genes that had been found earlier.
The combination of genetic, pathologic and molecular findings provide increasing evidence that the pathways identified through the cloning of different disease genes are interacting on different levels and share several major pathogenic mechanisms.
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ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system. Animal models have been invaluable tools for investigating the underlying mechanisms of the pathogenesis of PD and testing new potential symptomatic, neuroprotective and neurorestorative therapies. However, the usefulness of these models is dependent on how precisely they replicate the features of clinical PD with some studies now employing combined gene-environment models to replicate more of the affected pathways. The rotenone model of PD has become of great interest following the seminal paper by the Greenamyre group in 2000 (Betarbet et al., 2000). This paper reported for the first time that systemic rotenone was able to reproduce the two pathological hallmarks of PD as well as certain parkinsonian motor deficits. Since 2000, many research groups have actively used the rotenone model worldwide. This paper will review rotenone models, focusing upon their ability to reproduce the two pathological hallmarks of PD, motor deficits, extranigral pathology and non-motor symptoms. We will also summarize the recent advances in neuroprotective therapies, focusing on those that investigated non-motor symptoms and review rotenone models used in combination with PD genetic models to investigate gene-environment interactions.NeuroToxicology 12/2014; 46:101-116. DOI:10.1016/j.neuro.2014.12.002 · 3.05 Impact Factor
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ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects ~2% of the global population aged ≥65 years. Grb10-interacting GYF protein-2 (GIGYF2) can influence the development of PD through the regulation of insulin-like growth factor-1. The aim of the present meta-analysis study was to establish the contribution of GIGYF2 polymorphisms to PD. The study was conducted based on nine eligible studies consisting of 7,246 PD patients and 7,544 healthy controls. The results indicated that the GIGYF2 C.3630A>G polymorphism increased the risk of PD by 37% [P=0.008; odds ratio (OR), 1.37; 95% confidence interval (CI), 1.08-1.73] and that the GIGYF2 C.167G>A polymorphism was significantly associated with PD (P=0.003; OR, 3.67; 95% CI, 1.56-8.68). The meta-analyses of the other five GIGYF2 polymorphisms (C.1378C>A, C.1554G>A, C.2940A>G, C.1370C>A and C.3651G>A) did not reveal any significant associations. The present meta-analyses of the GIGYF2 genetic polymorphisms may provide a comprehensive overview of this PD candidate gene for future studies.11/2014; 2(6):886-892. DOI:10.3892/br.2014.324
Frontiers in Bioscience 01/2008; Volume(13):3288. DOI:10.2741/2926 · 4.25 Impact Factor