Abstract
Intense research efforts are currently directed at elucidating the etiology of Parkinson's disease (PD). One approach that has begun to shed light on the PD pathogenic pathways is the identification of disease genes through genetic linkage or association studies. These studies have revealed that several kinases may be involved in PD, as some PD genes encode kinases themselves while other PD genes are found in the same cellular pathways as kinases. Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2). Indeed, both α- syn and LRRK2 show genetic linkage as well as genetic association with PD, indicating their relevance to a large number of PD cases. Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD. Here we discuss the function of these kinases as well as progress in their validation as drug targets for the treatment of PD.
Keywords: Leucine rich repeat kinase 2, Polo like kinase 2, alpha-synuclein, PINK1, ROC-GTPase, Autophosphorylation, ROCO protein, D. melanogaster, enzyme linked immunosorbant assay, PLKS
CNS & Neurological Disorders - Drug Targets
Title: Kinases as Targets for Parkinson's Disease: From Genetics to Therapy
Volume: 10 Issue: 6
Author(s): Renee Vancraenenbroeck, Evy Lobbestael, Marc De Maeyer, Veerle Baekelandt and Jean-Marc Taymans
Affiliation:
Keywords: Leucine rich repeat kinase 2, Polo like kinase 2, alpha-synuclein, PINK1, ROC-GTPase, Autophosphorylation, ROCO protein, D. melanogaster, enzyme linked immunosorbant assay, PLKS
Abstract: Intense research efforts are currently directed at elucidating the etiology of Parkinson's disease (PD). One approach that has begun to shed light on the PD pathogenic pathways is the identification of disease genes through genetic linkage or association studies. These studies have revealed that several kinases may be involved in PD, as some PD genes encode kinases themselves while other PD genes are found in the same cellular pathways as kinases. Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2). Indeed, both α- syn and LRRK2 show genetic linkage as well as genetic association with PD, indicating their relevance to a large number of PD cases. Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD. Here we discuss the function of these kinases as well as progress in their validation as drug targets for the treatment of PD.
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Vancraenenbroeck Renee, Lobbestael Evy, De Maeyer Marc, Baekelandt Veerle and Taymans Jean-Marc, Kinases as Targets for Parkinson's Disease: From Genetics to Therapy, CNS & Neurological Disorders - Drug Targets 2011; 10 (6) . https://dx.doi.org/10.2174/187152711797247858
DOI https://dx.doi.org/10.2174/187152711797247858 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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