Parkinson's disease: genetics and pathogenesis.

@article{Shulman2011ParkinsonsDG,
  title={Parkinson's disease: genetics and pathogenesis.},
  author={J. Shulman and P. D. De Jager and M. 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
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Columbia University
November 2020 - December 2021

650 Citations

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The evolving mechanistic insight into the pathophysiology of PD and related conditions will contribute to the development of targeted and effective symptomatic treatments into disease-modifying therapies that will reduce the burden of these dreadful conditions. Expand
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The interplay between genetic predispositions and midbrain neuronal impairments in people living with PD is discussed and the understanding of robust cellular phenotypes across genetic cohorts of Parkinson’s patients may guide future personalized drug screens in preclinical research. Expand
Chapter 14 – Genetic Models of Parkinson’s Disease: Behavior, Signaling, and Pathological Features
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This chapter provides a comprehensive review of the pathological, neurochemical, and behavioral phenotypes in mouse genetic models of PD and identifies groups of animals with the greatest utility in identifying environmental agents that may alter the course of PD-associated symptoms. Expand
Biomarkers of Parkinson's disease and Dementia with Lewy bodies
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Recent availability of increasingly sophisticated bioinformatics technology has rendered development of fluid biomarkers feasible, opening the possibility of generally accessible blood or cerebrospinal fluid tests that could impact upon diagnosis, management, and research in PD, PDD, and DLB. Expand
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Behavioral, neurochemical and immunohistochemical analyses reveal that PD-linked mutations in Parkin and DJ-1 cause dysregulation of neurotransmitter systems beyond the nigrostriatal dopaminergic circuit and that loss-of-function mutations in parkin andDJ-1 lead to adaptive changes in dopamine and serotonin especially in the context of Gpx1 deficiency. Expand
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Progress and limitations of the multiple PD animal models available are reviewed and advances that could be implemented are identified to better understand pathological processes, improve disease outcome, and reduce dependence on animal models. Expand
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PD neurons show that elevated RBFOX1, a gene previously linked to neurodevelopmental diseases, underlies a pattern of alternative RNA-processing associated with PD-specific phenotypes, including oxidative stress vulnerability and altered neuronal activity. Expand
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Recent advances in the understanding of four PD-related gene products are reviewed, emphasizing the role of the PINK1/parkin pathway in regulating mitochondrial dynamics and mitophagy and pointing out converging pathways and future directions. Expand
Parkinson’s Disease in Saudi Patients: A Genetic Study
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This study suggests that mutations in the ORF of the screened genes are not a common cause of PD in Saudi population; however, these findings by no means exclude the possibility that other genetic events such as gene expression/dosage alteration may be more common nor does it eliminate the possibility of the involvement of novel genes. Expand
Mechanistic contributions of FBXO7 to Parkinson disease
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Recent research on FBXO7 is highlighted, which advances the knowledge of the etiopathological pathways and fills unexpected gaps therein, justifying the dedicated study of rare variants of PD. Expand
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References

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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
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TLDR
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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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