Genetic findings in Parkinson's disease and translation into treatment: a leading role for mitochondria?
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder and in most patients its aetiology remains unknown. Molecular genetic studies in familial forms of the disease identified key proteins involved in PD pathogenesis, and support a major role for mitochondrial dysfunction, which is also of significant importance to the common sporadic forms of PD. While current treatments temporarily alleviate symptoms, they do not halt disease progression. Drugs that target the underlying pathways to PD pathogenesis, including mitochondrial dysfunction, therefore hold great promise for neuroprotection in PD. Here we summarize how the proteins identified through genetic research (alpha-synuclein, parkin, PINK1, DJ-1, LRRK2 and HTRA2) fit into and add to our current understanding of the role of mitochondrial dysfunction in PD. We highlight how these genetic findings provided us with suitable animal models and critically review how the gained insights will contribute to better therapies for PD.
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, University of Antwerpen, Antwerpen, Belgium.
V
V
Bogaerts
J
J
Theuns
C
C
van Broeckhoven
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D017209:Apoptosis; D018450:Disease Progression; D004798:Enzymes / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
D004798:Enzymes; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein