Curr Med Chem. 2021 Nov 15; doi: 10.2174/0929867328666211115124639. Epub 2021 Nov 15.

Interplay Between Endocannabinoid System and Neurodegeneration: Focus on Polypharmacology.

Current medicinal chemistry

Francesca Seghetti, Silvia Gobbi, Federica Belluti, Angela Rampa, Alessandra Bisi

PMID: 34781863 DOI: 10.2174/0929867328666211115124639

Abstract

Pharmacological treatment of complex pathologies such as neurodegenerative diseases still represents a major challenge, due to the networked pathways involved in their onset and progression that may require equally complex therapeutic approaches. Polypharmacology, based on the simultaneous modulation of multiple targets involved in the disease, may offer the potential to increase effectiveness and reduce the drawbacks related to the use of drug combinations. Clearly, this approach requires both the knowledge of the systems responsible for disease development and the discovery of new attractive targets to be exploited to design a multitarget drug. Over the last years, an ever increasing interest has focused on the endocannabinoid system, implicated in the modulation of several physiological functions, among which neuroinflammation, a crucial process for most neurodegenerative diseases. In this respect, the cannabinoid receptor subtype 2 represents a promising therapeutic target, being overexpressed in microglia cells and thus involved in neuroinflammation. The indirect modulation of this system through the inhibition of the main enzymes responsible for endocannabinoids metabolism, namely fatty acid amide hydrolase and monoacylglycerol lipase, may also significantly affect neurodegenerative processes. The aim of this review is to give an overview of the opportunities posed by the endocannabinoid system for neurodegenerative diseases management, mainly focusing on the potential for a multitarget strategy.

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Keywords: Alzheimer's Disease; Endocannabinoid System; FAAH; MAGL; Neurodegenerative diseases; Parkinson’s Disease; cannabinoid receptors; multitarget drug

Publication Types

• Journal Article