Molecular mechanisms of selective dopaminergic neuronal death in Parkinson's disease.
Parkinson's disease (PD) is a progressive neurological disease caused by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Although PD has been heavily researched, the precise etiology of nigral cell loss is still unknown and, consequently, treatment is largely symptomatic rather than preventive. There are conflicting data regarding the mode of dopaminergic cell death in PD and, hence, this remains controversial. Several mutations in specific genes have recently been linked with hereditary forms of PD. Although none of these mutations are seen in idiopathic disease cases, the elucidation of these genetic defects sheds light on the nature of idiopathic PD. It is possible that dopaminergic neurogenesis also contributes to the etiology of idiopathic PD. In addition, intracellular as well as extracellular substances found in the SNc are believed to function as damaging pathogenetic factors. These factors, and the interactions among them, might hold the secret to the underlying causes of the selective death of dopaminergic neurons in PD.
Barzilai
Ari
A
Dept of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. barzilai@post.tau.ac.il
Melamed
Eldad
E
D016923:Cell Death; D004298:Dopamine / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000071617:Protein Deglycase DJ-1; D013378:Substantia Nigra / Q000473:pathology; D051843:Synucleins; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D015513:Oncogene Proteins; D051843:Synucleins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D043222:Ubiquitin Thiolesterase; D004298:Dopamine