Neuronal pathology in Parkinson's disease.
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra leading to the major clinical and pharmacological abnormalities of PD. In order to establish causal or protective treatments for PD, it is necessary to identify the cascade of deleterious events that lead to the dysfunction and death of dopaminergic neurons. Based on genetic, neuropathological, and biochemical data in patients and experimental animal models, dysfunction of the ubiquitin-proteasome pathway, protein aggregation, mitochondrial dysfunction, oxidative stress, activation of the c-Jun N-terminal kinase pathway, and inflammation have all been identified as important pathways leading to excitotoxic and apoptotic death of dopaminergic neurons. Toxin-based and genetically engineered animal models allow (1) the study of the significance of these aspects and their interaction with each other and (2) the development of causal treatments to stop disease progression.
Schulz
Jörg B
JB
Department of Neurodegeneration and Neurorestoration, DFG Research Center "Molecular Physiology of the Brain" and Center of Neurology, University of Göttingen, Waldweg 33, 37073 Göttingen, Germany. joerg.b.schulz@uni-tuebingen.de
Falkenburger
Björn H
BH
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology* / Q000628:therapy
D004298:Dopamine