Therapeutic Efficacy of Selegiline in Neurodegenerative Disorders and Neurological Diseases

Manuchair      Ebadi; Holly      Brown-Borg; Jun      Ren; Sushil      Sharma; Shaik      Shavali; Hesham      El ReFaey; Edward   C.   Carlson

Abstract

Selegiline inhibits the activity of monoamine oxidase B, enhances the release of dopamine, blocks the uptake of dopamine, acts as a calmodulin antagonist, and enhances the level of cyclic AMP, which in turn protects dopaminergic neurons. It possesses cognition- enhancing functions, rejuvenates serum insulin-like growth factor I in aged rats, and enhances life expectancy in rodents. Selegiline possesses neurotrophic-like actions, and rescues axotomized motorneurons independent of monoamine oxidase B inhibition. It enhances the synthesis of nerve growth factor, protects dopaminergic neurons from glutamate-mediated neurotoxicity, and protects dopaminergic neurons from toxic factors present in the spinal fluid of parkinsonian patients, and the said effect may be mediated via elaborating brain derived neurotrophic factor. Selegiline increases the striatal superoxide dismutase, protects against peroxynitrite- and nitric oxide-induced apoptosis, and guards dopaminergic neurons from toxicity induced by glutathione depletion. It stimulates the biosynthesis of interleukin 1-β and interleukin-6, is an immunoenhancing substance, possesses antiapoptotic actions, and is neuroprotectant in nature. Selegiline has been shown to be efficacious in Parkinsons disease, global ischemia, Gille de la Tourette syndrome, and narcolepsy. Its therapeutic efficacy in Alzheimers disease remains uncertain. In Alzheimers disease, short term studies of selegiline suggest a beneficial effect; whereas long term studies are less convincing.

Keywords: MPTP, 6-hydroxydopamine, Selegiline, Rasagiline, Monoamine Oxidase B, Parkinson's Disease, Alzheimer's Disease, Neurorestoration, Neuroprotection