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Levodopa induces apoptosis in cultured neuronal cells—A possible accelerator of nigrostriatal degeneration in Parkinson's disease?
Author(s) -
Ziv Ilan,
ZilkhaFalb Rina,
Offen Daniel,
Shirvan Anat,
Barzilai Ari,
Melamed Eldad
Publication year - 1997
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.870120105
Subject(s) - levodopa , apoptosis , parkinson's disease , dopaminergic , programmed cell death , nigrostriatal pathway , neuroscience , biology , microbiology and biotechnology , substantia nigra , chemistry , dopamine , medicine , disease , biochemistry
Apoptosis is an active, intrinsic cell suicide program. We recently suggested that it may have a role in the death of nigrostriatal dopaminergic neurons in Parkinson's disease (PD). We now report that levodopa, the current major therapy for PD, is a potent inducer of apoptosis in cultured postmitotic chick sympathetic neurons. Levodopa, in a concentration range of 0.01–0.3 m M , caused the characteristic apoptotic cascade of cell shrinkage, massive membrane blebbing, and nuclear fragmentation, as evident by nuclear flow cytometry and fluorescence microscopy. Levodopa‐induced apoptosis was inhibited by antioxidants, indicating that it may be mediated by autooxidation‐reactive species. Levodopa treatment for PD may therefore constitute an additional challenge for the defective apoptosis‐inhibiting systems in the nigrostriatal neurons. Despite reassuring data from some, but not all, previous studies, these findings suggest that the possible in vivo toxic effects of levodopa on the survival of the remaining nigral neurons should be further explored.