Advances in the genetics of Parkinson disease

@article{Trinh2013AdvancesIT,
  title={Advances in the genetics of Parkinson disease},
  author={Joanne Trinh and Matthew J Farrer},
  journal={Nature Reviews Neurology},
  year={2013},
  volume={9},
  pages={445-454}
}
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… Expand
Chapter 42 - Parkinson's Disease: Genetics
Since the mid-1990s, genetic studies have advanced our understanding of Parkinson's disease (PD) etiology, showing it to be a polygenic disorder with a heterogeneous phenotypic spectrum. Mutations inExpand
Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease
TLDR
This work focuses on familial forms of late-onset parkinsonism that most closely resemble idiopathic Parkinson's disease and proposes that cellular processes constitute one pathway to pathogenesis and suggests that neuroprotection, as an adjunct to current symptomatic treatments, need not remain an elusive goal. Expand
Progress in unraveling the genetic etiology of Parkinson disease in a genomic era.
TLDR
With an estimated 30% of trait variance currently unexplained, tackling current limitations will further expedite gene discovery and lead to increased application of these genetic insights in molecular diagnostics using gene panel and exome sequencing strategies. Expand
Genetics and genomics of Parkinson’s disease
TLDR
In more typical late-onset PD, chronic dysfunction in synaptic transmission, early endosomal trafficking and receptor recycling, as well as chaperone-mediated autophagy, provide a unifying synthesis of the molecular pathways involved. Expand
Analysis of copy number variation and disease mechanisms underlying Parkinson’s disease
TLDR
A cellular model of PD was created by decreasing the expression of PINK1 in SH-SY5Y neuroblastoma cells and the protective effects of curcumin was tested on this model in the presence and absence of a known stressor, paraquat. Expand
Genetics of neurodegenerative diseases: an overview.
TLDR
Major developments in the field to date are reviewed, highlighting overarching historic trends and general insights, and individual genetic profiling will also be increasingly relevant in a clinical context, with implications for patient care in line with the proposed ideal of personalized medicine. Expand
Pathways to Parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson's disease.
TLDR
Evidence for a role of PD proteins in microglial activation and regulation of the autophagy-lysosome system that is dependent on microtubule transport in neurons means there are at least two non-mutually exclusive pathways that include both non-cell-autonomous and cell-aut autonomous mechanisms in the PD brain. Expand
RNA metabolism in the pathogenesis of Parkinson׳s disease
TLDR
It is anticipated that continued studies on the role of RNA metabolism in Parkinson's disease will offer unifying mechanisms for understanding the cause of neuronal dysfunction and degeneration and facilitate the development of novel and rational strategies for treating this debilitating disease. Expand
Genetic causes of Parkinson's disease and their links to autophagy regulation.
TLDR
Recent progress in understanding the influence of disease risk genes on cellular functions, specifically, autophagy pathways is reviewed and the prospect of intervening autophagic pathways as a potential strategy to treat Parkinson's disease is discussed. Expand
A mitocentric view of Parkinson's disease.
TLDR
It is proposed that subtle mitochondrial defects in combination with other insults trigger the onset and progression of disease, in both familial and idiopathic PD. Expand
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