Parkinson's disease: genetics and pathogenesis.

  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},
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… 
Genetics of Parkinson’s disease and related disorders
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.
Genetic predispositions of Parkinson’s disease revealed in patient-derived brain cells
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.
Animal Models of Autosomal Recessive Parkinsonism
The current status of PD modeling using mouse, rat and non-mammalian models is outlined, focusing on animal models for autosomal recessive PD.
Biomarkers of Parkinson's disease and Dementia with Lewy bodies
Molecular insights into Parkinson's disease.
Parkinson’s Disease in Saudi Patients: A Genetic Study
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.
Mechanistic contributions of FBXO7 to Parkinson disease
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.


Parkinson's Disease Mechanisms and Models
A susceptibility locus for Parkinson's disease maps to chromosome 2p13
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).
Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
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.
Increased susceptibility to sporadic Parkinson's disease by a certain combined α‐synuclein/apolipoprotein E genotype
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.
The genetics of Parkinson's syndromes: a critical review.
Epidemiology of Parkinson's disease
Mendelian forms of Parkinson's disease.
  • T. Gasser
  • Biology
    Biochimica et biophysica acta
  • 2009
Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data.
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.