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Impact of recent genetic findings in Parkinson's disease.
Curr Opin Neurol. 2007 Aug; 20(4):453-64.CO

Abstract

PURPOSE OF REVIEW

Parkinson's disease is the second most common age-related neurodegenerative disorder and is characterized clinically by classical parkinsonism and pathologically by selective loss of dopaminergic neurons in the substantia nigra and Lewy bodies. Although for most classical parkinsonism the etiology is unknown, a clear genetic component has been determined in a minority. Mutations in five causative genes combined [alpha-Synuclein (SNCA), Parkin, PTEN-induced kinase 1 (PINK1), DJ-1, Leucine-rich repeat kinase 2 (LRRK2)] account for 2-3% of all cases with classical parkinsonism, often clinically indistinguishable from idiopathic Parkinson's disease.

RECENT FINDINGS

The functional role of PINK1 and LRRK2 as kinases has been clearly established. Further, mutations in the ATP13A2 gene have been linked to Kufor-Rakeb syndrome (PARK9), a form of atypical parkinsonism. ATP13A2 encodes a lysosomal ATPase and shows elevated expression levels in the brains of sporadic patients, suggesting a potential role in the more common idiopathic Parkinson's disease. Finally, first promising pilot studies have been performed to identify differentially expressed genes and proteins as biomarkers for parkinsonism.

SUMMARY

The identification of single genes and their functional characterization has enhanced our understanding of the pathogenesis of parkinsonism, has led to improvement of diagnostic tools for genetic parkinsonism, and allows for the purposeful consideration of novel therapeutic targets.

Authors+Show Affiliations

Departments of Neurology and Human Genetics, Lübeck University, Lübeck, Germany. christine.klein@neuro.uni-luebeck.deNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17620882

Citation

Klein, Christine, and Katja Lohmann-Hedrich. "Impact of Recent Genetic Findings in Parkinson's Disease." Current Opinion in Neurology, vol. 20, no. 4, 2007, pp. 453-64.
Klein C, Lohmann-Hedrich K. Impact of recent genetic findings in Parkinson's disease. Curr Opin Neurol. 2007;20(4):453-64.
Klein, C., & Lohmann-Hedrich, K. (2007). Impact of recent genetic findings in Parkinson's disease. Current Opinion in Neurology, 20(4), 453-64.
Klein C, Lohmann-Hedrich K. Impact of Recent Genetic Findings in Parkinson's Disease. Curr Opin Neurol. 2007;20(4):453-64. PubMed PMID: 17620882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of recent genetic findings in Parkinson's disease. AU - Klein,Christine, AU - Lohmann-Hedrich,Katja, PY - 2007/7/11/pubmed PY - 2007/12/28/medline PY - 2007/7/11/entrez SP - 453 EP - 64 JF - Current opinion in neurology JO - Curr Opin Neurol VL - 20 IS - 4 N2 - PURPOSE OF REVIEW: Parkinson's disease is the second most common age-related neurodegenerative disorder and is characterized clinically by classical parkinsonism and pathologically by selective loss of dopaminergic neurons in the substantia nigra and Lewy bodies. Although for most classical parkinsonism the etiology is unknown, a clear genetic component has been determined in a minority. Mutations in five causative genes combined [alpha-Synuclein (SNCA), Parkin, PTEN-induced kinase 1 (PINK1), DJ-1, Leucine-rich repeat kinase 2 (LRRK2)] account for 2-3% of all cases with classical parkinsonism, often clinically indistinguishable from idiopathic Parkinson's disease. RECENT FINDINGS: The functional role of PINK1 and LRRK2 as kinases has been clearly established. Further, mutations in the ATP13A2 gene have been linked to Kufor-Rakeb syndrome (PARK9), a form of atypical parkinsonism. ATP13A2 encodes a lysosomal ATPase and shows elevated expression levels in the brains of sporadic patients, suggesting a potential role in the more common idiopathic Parkinson's disease. Finally, first promising pilot studies have been performed to identify differentially expressed genes and proteins as biomarkers for parkinsonism. SUMMARY: The identification of single genes and their functional characterization has enhanced our understanding of the pathogenesis of parkinsonism, has led to improvement of diagnostic tools for genetic parkinsonism, and allows for the purposeful consideration of novel therapeutic targets. SN - 1350-7540 UR - https://www.unboundmedicine.com/medline/citation/17620882/Impact_of_recent_genetic_findings_in_Parkinson's_disease_ L2 - https://doi.org/10.1097/WCO.0b013e3281e6692b DB - PRIME DP - Unbound Medicine ER -