IMR Press / FBL / Volume 13 / Issue 13 / DOI: 10.2741/3069

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
The neuroprotective mechanism of action of the multimodal drug ladostigil
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1 Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute, Technion-Faculty of Medicine, Haifa, 31096, Israel

*Author to whom correspondence should be addressed.

 

Front. Biosci. (Landmark Ed) 2008, 13(13), 5131–5137; https://doi.org/10.2741/3069
Published: 1 May 2008
Abstract

The recent therapeutic approach in which drug candidates are designed to possess diverse pharmacological properties and act on multiple targets has stimulated the development of the multimodal drug, ladostigil (TV3326) ((N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate). Ladostigil combines neuroprotective effects with monoamine oxidase -A and -B and cholinesterase inhibitory activities in a single molecule, as a potential treatment for Alzheimer's disease (AD) and Lewy Body disease. Preclinical studies show that ladostigil has antidepressant and anti-AD activities and the clinical development is planned for these dementias. In this review, we discuss the multimodal effects of ladostigil in terms of neuroprotective molecular mechanism in vivo and in vitro, which include the amyloid precursor protein processing; activation of protein kinase C and mitogen-activated protein kinase pathways; regulation of the Bcl-2 family members; inhibition of cell death markers and up-regulation of neurotrophic factors. Altogether, these scientific findings make ladostigil a potentially valuable drug for the treatment of AD.

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