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.
Export Options
About this article
Cite this article as:
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Role of Hydrogen Sulfide in Systemic and Pulmonary Hypertension: Cellular Mechanisms and Therapeutic Implications
Cardiovascular & Hematological Agents in Medicinal Chemistry Immunotherapies for Parkinson’s Disease: Progression of Clinical Development
CNS & Neurological Disorders - Drug Targets Sphingolipid Metabolism and Drug Resistance in Hematological Malignancies
Anti-Cancer Agents in Medicinal Chemistry Targeting Proliferating Cell Nuclear Antigen (PCNA) as an Effective Strategy to Inhibit Tumor Cell Proliferation
Current Cancer Drug Targets The Pro-Apoptotic Substance Thapsigargin Selectively Stimulates Re-Growth of Brain Capillaries
Current Neurovascular Research The Involvement of Post-Translational Modifications in Alzheimer's Disease
Current Alzheimer Research Neuropeptide FF Inhibits LPS-Mediated Osteoclast Differentiation of RAW264.7 Cells
Protein & Peptide Letters The Molecular and Pharmacological Mechanisms of HIV-Related Neuropathic Pain
Current Neuropharmacology n-3 Fatty Acids: Role in Neurogenesis and Neuroplasticity
Current Medicinal Chemistry Hydrogen Sulphide: Biopharmacological Roles in the Cardiovascular System and Pharmaceutical Perspectives
Current Medicinal Chemistry Current Concepts and Future Directions in Radioimmunotherapy
Current Drug Discovery Technologies Artificial Intelligence, Big Data and Machine Learning Approaches in Precision Medicine & Drug Discovery
Current Drug Targets Co-Treatment With Copper Compounds Dramatically Decreases Toxicities Observed With Cisplatin Cancer Therapy And The Anticancer Efficacy Of Some Copper Chelates Supports The Conclusion That Copper Chelate Therapy May Be Markedly More Effective And Less Toxic Than Cisplatin Therapy
Current Medicinal Chemistry Induction of Tumour Cell Senescence: A New Strategy in Anticancer Treatment
Medicinal Chemistry Reviews - Online (Discontinued) Monoamine Oxidase Inhibitors as Neuroprotective Agents in Age-Dependent Neurodegenerative Disorders
Current Pharmaceutical Design BK Channel Modulators: A Comprehensive Overview
Current Medicinal Chemistry Angiogenesis and Metastasis Inhibitors for the Treatment of Malignant Melanoma
Mini-Reviews in Medicinal Chemistry Low Doses Naltrexone: The Potential Benefit Effects for its Use in Patients with Cancer
Current Drug Research Reviews Targeting Cell Death in Tumors by Activating Caspases
Current Cancer Drug Targets Oxidative Stress-Induced Necrotic Cell Death via Mitochondira-Dependent Burst of Reactive Oxygen Species
Current Neurovascular Research