title: Parkinson's disease.
abstract: Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by a profound and selective loss of nigrostriatal dopaminergic neurons. Clinical manifestations of this complex disease include motor impairments involving resting tremor, bradykinesia, postural instability, gait difficulty and rigidity. Current medications only provide symptomatic relief and fail to halt the death of dopaminergic neurons. A major hurdle in development of neuroprotective therapies are due to limited understanding of disease processes leading to death of dopaminergic neurons. While the etiology of dopaminergic neuronal demise is elusive, a combination of genetic susceptibilities and environmental factors seems to play a critical role. The majority of PD cases are sporadic however, the discovery of genes linked to rare familial forms of disease (encoding alpha-synuclein, parkin, DJ-1, PINK-1 and LRRK2) and studies from experimental animal models has provided crucial insights into molecular mechanisms in disease pathogenesis and identified probable targets for therapeutic intervention. Recent findings implicate mitochondrial dysfunction, oxidative damage, abnormal protein accumulation and protein phosphorylation as key molecular mechanisms compromising dopamine neuronal function and survival as the underlying cause of pathogenesis in both sporadic and familial PD. In this review we provide an overview of the most relevant findings made by the PD research community in the last year and discuss how these significant findings improved our understanding of events leading to nigrostriatal dopaminergic degeneration, and identification of potential cell survival pathways that could serve as targets for neuroprotective therapies in preventing this disabling neurological illness.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, A-501, New York, NY 10021, USA. bot2003@med.cornell.edu
authors.forename: Bobby
authors.initials: B
authors.lastname: Thomas
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human