Drug Design and Discovery in Alzheimer’s Disease

Republished Version of Frontiers in Drug Design and Discovery Volume 6

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Multifunctional Enzyme Inhibition for Neuroprotection - A Focus on MAO, NOS, and AChE Inhibitors

Pp. 291-365 (75)

Jacques Joubert, Jacobus P. Petzer, Louis H.A. Prins, Benjamin P. Repsold and Sarel F. Malan

Abstract

Neurodegenerative disorders are known to be multifactorial in nature and current research focus has moved from a ‘one-drug-one-target approach’ to that of drugs which are able to act at various relevant biological targets. These drugs are designed to address more than one etiological target, thereby increasing therapeutic effect and patient compliance and may lower the likelihood of encountering unwanted side-effects. Monoamine oxidase (MAO), nitric oxide synthase (NOS), and acetylcholinesterase (AChE) are enzymes that have long been associated as potential targets for neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. The selective inhibition of the abovementioned enzymes and other relevant CNS targets may provide promising strategies in the development of multifunctional neuroprotective therapeutic agents for the treatment/prevention of neurodegenerative disorders.

Keywords:

Acetylcholinesterase, Alzheimer’s and Parkinson’s disease, drug design, monoamine oxidase, multi-target-directed ligands, neurodegenerative disorders, nitric oxide synthase.

Affiliation:

School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa.