Impact of recent genetic findings in Parkinson's disease.

@article{citeulike:2734818, 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.}, address = {Departments of Neurology and Human Genetics, L\"{u}beck University, L\"{u}beck, Germany. christine.klein@neuro.uni-luebeck.de}, author = {Klein, C. and Lohmann-Hedrich, K. }, citeulike-article-id = {2734818}, doi = {http://dx.doi.org/10.1097/WCO.0b013e3281e6692b}, issn = {1350-7540}, journal = {Current opinion in neurology}, keywords = {atp13a2, genetics, lrrk2, parkinsons, pink1}, month = {August}, number = {4}, pages = {453--464}, posted-at = {2008-04-29 17:18:05}, priority = {2}, title = {Impact of recent genetic findings in Parkinson's disease.}, url = {http://dx.doi.org/10.1097/WCO.0b013e3281e6692b}, volume = {20}, year = {2007} }

TY - JOUR ID - citeulike:2734818 L3 - citeulike-article-id:2734818 TI - Impact of recent genetic findings in Parkinson's disease. JF - Current opinion in neurology VL - 20 IS - 4 SP - 453 EP - 464 AD - Departments of Neurology and Human Genetics, Lübeck University, Lübeck, Germany. christine.klein@neuro.uni-luebeck.de SN - 1350-7540 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. KW - atp13a2 KW - genetics KW - lrrk2 KW - parkinsons KW - pink1 AU - Klein, C AU - Lohmann-Hedrich, K PY - 2007/08// UR - http://dx.doi.org/10.1097/WCO.0b013e3281e6692b ER -