Neuroprotection in the MPTP Parkinsonian C57BL/6 mouse model by a compound isolated from tobacco.
Epidemiological evidence suggests a lower incidence of Parkinson's disease in smokers than in nonsmokers. This evidence, together with the lower levels of brain monoamine oxidase (MAO) activity in smokers and the potential neuroprotective properties of MAO inhibitors, prompted studies which led to the isolation and characterization of 2,3,6-trimethyl-1,4-naphthoquinone (TMN), an MAO-A and MAO-B inhibitor which is present in tobacco and tobacco smoke. Results of experiments reported here provide evidence that this compound protects against the MPTP-mediated depletion of neostriatal dopamine levels in the C57BL/6 mouse. These results support the hypothesis that the inhibition of MAO by constituents of tobacco smoke may be related to the decreased incidence of Parkinson's disease in smokers.
Castagnoli
K P
KP
Harvey W. Peters Center, Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061-0212, USA. kcastagn@vt.edu
Steyn
S J
SJ
Petzer
J P
JP
Van der Schyf
C J
CJ
Castagnoli
N
N
D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000187:drug effects* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D009285:Naphthoquinones / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D017072:Neostriatum / Q000378:metabolism; D018696:Neuroprotective Agents / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000517:prevention & control*; D010936:Plant Extracts
C432524:2,3,6-trimethyl-1,4-naphthoquinone; D008996:Monoamine Oxidase Inhibitors; D009285:Naphthoquinones; D018696:Neuroprotective Agents; D010936:Plant Extracts; D008995:Monoamine Oxidase; D004298:Dopamine