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Therapeutic Efficacy of Selegiline in Neurodegenerative Disorders and Neurological Diseases

[ Vol. 7 , Issue. 11 ]

Author(s):

Manuchair Ebadi, Holly Brown-Borg, Jun Ren, Sushil Sharma, Shaik Shavali, Hesham El ReFaey and Edward C. Carlson   Pages 1513 - 1529 ( 17 )

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

Affiliation:

Chester Fritz Distinguished Professor, Professor of Pharmacology and of Clinical Neuroscience, Associate Dean for Research and Program Development, School of Medicine,Director, Center of Excellence in Neurosciences, University of North Dakota,Associate Vice President for Medical Research, University of North Dakota, USA.



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