Discoveries from the Bench to the Bedside

Why Do We Need Multifunctional Neuroprotective and Neurorestorative Drugs for Parkinson’s and Alzheimer’s Disorders?

Mussa Youdim

Abstract

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of pa-tients suffering from PD and AD, and all drug treatments are symptomatic and monomodal in their action. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that result in neuronal death and predisposition to depression and eventual dementia, and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) is the development and use of multifunctional pharmaceuticals which can act at different brain regions and neurons. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD, some of which are under development. The compounds discussed originate from synthetic chemistry as well as from natural sources. KEY WORDS: Rasagiline multimodal drugs, antiapoptotic, neuroprotection, neurorestoration, Parkinson’s disease, Alzheimer’s disease

Rambam Maimonides Med J 2010;1(2):e0011