Activation of the proopiomelanocortin gene with ketoconazole as a treatment for Parkinson's disease: a new hypothesis.

Parkinson's disease is a neurodegenerative process characterized by progressive degeneration of the substantia nigra and concurrent loss of neuromelanin in these structures. The present hypothesis suggests that progression of Parkinson's disease may be reduced by enhancing the regional levels of neuroprotective factors derived from proopiomelanocortin (POMC). One practical means to accomplish this goal may be administration of ketoconazole or other inhibitors of corticosteroid synthesis at doses sufficient to stimulate hypophyseal secretion of POMC. The POMC constituents adrenocorticotropic hormone (ACTH) and melanocycle-stimulating hormone (MSH), which mobilize neuromelanin generation and lipotropins, those motivating lipid components of neuromelanin and endorphin, which then together stimulate and protect neural components of the substantia nigra.