TY - JOUR
T1 - Is there a rationale for neuroprotection against dopamine toxicity in Parkinson's disease?
AU - Barzilai, Ari
AU - Melamed, Eldad
AU - Shirvan, Anat
PY - 2001
Y1 - 2001
N2 - Parkinson's disease is a progressive neurological disease caused by rather selective degeneration of the dopaminergic neurons in the substantia nigra. Though subject to intensive research, the etiology of this nigral loss is still undetermined and treatment is basically symptomatic. The current major hypothesis is that nigral neuronal death in PD is due to excessive oxidative stress generated by auto and enzymatic oxidation of the endogenous neurotransmitter dopamine (DA), the formation of neuromelanin (NM) and the presence of a high concentration of iron. In this review article although we concisely describe the effects of NM and iron on neuronal survival, we mainly focus on the molecular mechanisms of DA-induced apoptosis. DA exerts its toxic effects through its oxidative metabolites either in vitro or in vivo. The oxidative metabolites then activate a very intricate web of signals, which culminate in cell death. The signal transduction pathways and genes, which are associated with DA toxicity are described in detail.
AB - Parkinson's disease is a progressive neurological disease caused by rather selective degeneration of the dopaminergic neurons in the substantia nigra. Though subject to intensive research, the etiology of this nigral loss is still undetermined and treatment is basically symptomatic. The current major hypothesis is that nigral neuronal death in PD is due to excessive oxidative stress generated by auto and enzymatic oxidation of the endogenous neurotransmitter dopamine (DA), the formation of neuromelanin (NM) and the presence of a high concentration of iron. In this review article although we concisely describe the effects of NM and iron on neuronal survival, we mainly focus on the molecular mechanisms of DA-induced apoptosis. DA exerts its toxic effects through its oxidative metabolites either in vitro or in vivo. The oxidative metabolites then activate a very intricate web of signals, which culminate in cell death. The signal transduction pathways and genes, which are associated with DA toxicity are described in detail.
KW - Apoptosis
KW - Dopamine
KW - L-DOPA
KW - Oxidative stress
KW - Parkinson's disease
KW - Semaphorins
UR - http://www.scopus.com/inward/record.url?scp=0034844226&partnerID=8YFLogxK
U2 - 10.1023/A:1010991020245
DO - 10.1023/A:1010991020245
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???
AN - SCOPUS:0034844226
SN - 0272-4340
VL - 21
SP - 215
EP - 235
JO - Cellular and Molecular Neurobiology
JF - Cellular and Molecular Neurobiology
IS - 3
ER -