TY - JOUR
T1 - Excitotoxicity of l-DOPA and 6-OH-DOPA
T2 - Implications for Parkinson's and Huntington's diseases
AU - Olney, John W.
AU - Zorumski, Charles F.
AU - Stewart, Gregory R.
AU - Price, Madelon T.
AU - Wang, Guangjian
AU - Labruyere, Joann
PY - 1990/6
Y1 - 1990/6
N2 - Despite several decades of research aimed at elucidating the mechanisms underlying neuronal degeneration in Parkinson's and Huntington's diseases, these mysteries remain unfathomed. The brain contains high concentrations of the putative transmitters, glutamate and aspartate, which have neurotoxic (excitotoxic) potential and are thought to cause neuronal degeneration in certain acute neurological disorders. However, no mechanism has been identified by which these diffusely distributed agents might cause the regionally selective patterns of neuronal degeneration characterizing Parkinson's and Huntington's diseases. Here we report that l-DOPA, the natural precursor to dopamine, is a weak excitotoxin and its ortho-hydroxylated derivative, 6-OH-DOPA, is a powerful excitotoxin. We propose that an excitotoxic process mediated by l-DOPA or an acidic derivative such as 6-OH-DOPA might be responsible for degeneration of nigral neurons in Parkinson's disease or striatal neurons in Huntington's disease.
AB - Despite several decades of research aimed at elucidating the mechanisms underlying neuronal degeneration in Parkinson's and Huntington's diseases, these mysteries remain unfathomed. The brain contains high concentrations of the putative transmitters, glutamate and aspartate, which have neurotoxic (excitotoxic) potential and are thought to cause neuronal degeneration in certain acute neurological disorders. However, no mechanism has been identified by which these diffusely distributed agents might cause the regionally selective patterns of neuronal degeneration characterizing Parkinson's and Huntington's diseases. Here we report that l-DOPA, the natural precursor to dopamine, is a weak excitotoxin and its ortho-hydroxylated derivative, 6-OH-DOPA, is a powerful excitotoxin. We propose that an excitotoxic process mediated by l-DOPA or an acidic derivative such as 6-OH-DOPA might be responsible for degeneration of nigral neurons in Parkinson's disease or striatal neurons in Huntington's disease.
UR - http://www.scopus.com/inward/record.url?scp=0025371344&partnerID=8YFLogxK
U2 - 10.1016/0014-4886(90)90134-E
DO - 10.1016/0014-4886(90)90134-E
M3 - Article
C2 - 1972067
AN - SCOPUS:0025371344
SN - 0014-4886
VL - 108
SP - 269
EP - 272
JO - Experimental Neurology
JF - Experimental Neurology
IS - 3
ER -