title: Parkinson's disease: From human genetics to clinical trials.
abstract: Combining genetic insights into the pathogenesis of Parkinson's disease (PD) with findings from animal and cellular models of this disorder has advanced our understanding of the pathways that lead to the characteristic degeneration of dopaminergic neurons in the brain's nigrostriatal pathway. This has fueled an increase in candidate compounds designed to modulate these pathways and to alter the processes underlying neuronal death in this disorder. Using mitochondrial quality control and the macroautophagy/lysosomal pathways as examples, we discuss the pipeline from a comprehensive genetic architecture for PD through to clinical trials for drugs targeting pathways linked to neurodegeneration in PD. We also identify opportunities and pitfalls on the road to a clinically effective disease-modifying treatment for this disease.
authors.affiliation: Department of Diagnostics Discovery, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Marcel P
authors.initials: MP
authors.lastname: van der Brug
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.affiliation: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Centre for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.affiliation: School of Pharmacy, University of Reading, Reading RG6 6AP, UK. Centre for Integrated Neuroscience and Neurodynamics, University of Reading, Reading RG6 6AP, UK. Department of Molecular Neuroscience, UCL Institute of Neurology, Queen's Square, London WC1N 3BG, UK. p.a.lewis@reading.ac.uk.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Lewis
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D015195:Drug Design; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics*; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D004298:Dopamine