Rasagiline: an anti-Parkinson drug with neuroprotective activity.
Mitochondria are now recognized as potent integrators and co-ordinators of cell survival/death and apoptosis. Therefore, they are pharmacological targets for induction or correction of excessive cell death in human pathology, which includes cancer and the neurodegenerative disorders Parkinson's and Alzheimer's disease. One such agent is the anti-Parkinson drug, rasagiline, a novel neuroprotective-antiapoptotic second-generation potent irreversible selective inhibitor of monoamine oxidase B. It prevents the neurotoxin-initiated demise of mitochondria via modulation of cell survival/death Bcl-2 family proteins, Bcl-2-Bax, at the mitochondria permeability transition pore, which regulates voltage-dependent anion channels. It may also induce long-term potentiation - a consequence of its protein kinase C-dependent mitogen-activated protein kinase pathway activation. Rasagiline, unlike selegiline, is devoid of sympathomimetic action and is not metabolized to neurotoxic methamphetamine, but to aminoindan. Its neuroprotective activity is attributed to the aminoindan and propargylamine moieties and structural resemblance to certain metabotrophic glutamate 1 receptor antagonists. Ragagiline has been chosen for neuroprotective studies by the National Institutes of Health as a possible disease-modifying agent.
Youdim
Moussa Bh
MB
EveTopf and National Parkinson Foundation Centers, Centers of Excellence for Neurodegenerative Diseases Research, Technion Faculty of Medicine, Efron St., PO Box 9697, Haifa 31096, Israel. youdim@tx.technion.ac.il