Advances in the genetics of Parkinson disease - PubMed (original) (raw)
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Advances in the genetics of Parkinson disease
Joanne Trinh et al. Nat Rev Neurol. 2013 Aug.
Abstract
Parkinson disease (PD) is a multifactorial neurodegenerative disease that was long considered the result of environmental factors. In the past 15 years, however, a genetic aetiology for PD has begun to emerge. Here, we review results from linkage and next-generation sequencing studies of familial parkinsonism, as well as candidate gene and genome-wide association findings in sporadic PD. In these studies, many of the genetic findings overlap, despite different designs and study populations, highlighting novel therapeutic targets. The molecular results delineate a sequence of pathological events whereby deficits in synaptic exocytosis and endocytosis, endosomal trafficking, lysosome-mediated autophagy and mitochondrial maintenance increase susceptibility to PD. These discoveries provide the rationale, molecular insight and research tools to develop neuroprotective and disease-modifying therapies.
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References
- Neurogenetics. 2012 Aug;13(3):281-5 - PubMed
- Science. 1997 Jun 27;276(5321):2045-7 - PubMed
- Ann N Y Acad Sci. 2003 Jun;991:1-14 - PubMed
- Mov Disord. 2012 Aug;27(9):1104-10 - PubMed
- Nat Genet. 2011 May;43(5):436-41 - PubMed
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