Parkinson's disease: genetics and pathogenesis.

@article{Shulman2011ParkinsonsDG,
  title={Parkinson's disease: genetics and pathogenesis.},
  author={Joshua M. Shulman and Philip L. De Jager and Mel B Feany},
  journal={Annual review of pathology},
  year={2011},
  volume={6},
  pages={
          193-222
        }
}
Recent investigation into the mechanisms of Parkinson's disease (PD) has generated remarkable insight while simultaneously challenging traditional conceptual frameworks. Although the disease remains defined clinically by its cardinal motor manifestations and pathologically by midbrain dopaminergic cell loss in association with Lewy bodies, it is now recognized that PD has substantially more widespread impact, causing a host of nonmotor symptoms and associated pathology in multiple regions… Expand

Paper Mentions

Interventional Clinical Trial
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References

SHOWING 1-10 OF 182 REFERENCES
A susceptibility locus for Parkinson's disease maps to chromosome 2p13
TLDR
A different genetic locus that appears to be involved in the development of parkinsonism closely resembling sporadic PD is described including a similar mean age of onset (59 years in the families, 59.7 years in sporadic PD; ref. 12). Expand
Parkinson's Disease Mechanisms and Models
TLDR
PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process. Expand
Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease
TLDR
The cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain is described and this protein is named dardarin, derived from the Basque word dardara, meaning tremor, because of the tremor observed in PD. Expand
Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria
TLDR
The diagnostic criteria for the neuropathological assessment of PD are discussed and need to be validated through an iterative process that could help with their refinement, and future directions for neuropathology research on PD are suggested. Expand
Increased susceptibility to sporadic Parkinson's disease by a certain combined α‐synuclein/apolipoprotein E genotype
TLDR
A highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. Expand
The genetics of Parkinson's syndromes: a critical review.
TLDR
It is argued that this designation of PARK loci is misleading and that if the authors seek to understand the pathogenesis, they should study the genetics of Lewy body diseases: these include not only idiopathic Parkinson's disease, but also such disparate syndromes as Hallevorden-Spatz disease and Niemann-Pick Type C. Expand
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
TLDR
The identification of two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families provide a direct molecular link between mitochondria and the pathogenesis of PD. Expand
Mendelian forms of Parkinson's disease.
  • T. Gasser
  • Biology, Medicine
  • Biochimica et biophysica acta
  • 2009
TLDR
Evidence is emerging that at least some of these genes may play a direct role in the etiology of the common sporadic form of PD, and it is likely that the cellular pathways identified in rare monogenic variants of the disease also shed light on the molecular pathogenesis in typical sporadic PD. Expand
Epidemiology of Parkinson's disease
TLDR
This article reviews what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies and suggests that major gene mutations cause only a small proportion of all cases. Expand
Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data.
TLDR
The data suggest that parkinsonism caused by mutations in LRRK2 is likely to represent the commonest locus for autosomal dominant Parkinson's disease with a phenotype, pathology and in vivo imaging similar to idiopathic, late-onset Parkinson’s disease. Expand
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