The endocannabinoid system: a putative role in neurodegenerative diseases

Abstract

Background: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations.

Objectives: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases.

Materials and methods: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed.

Results: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington's, Parkinson's and Alzheimer's diseases.

Conclusions: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology.

Keywords: Cannabinoid Receptors; Endocannabinoids; Neurodegenerative Diseases.

Figure 1.. Anandamide (AEA) Synthesis Is Started by Enzyme N-acyltransferase (NAT), That Catalyzes the Reaction of Phosphatidyletanolamine With Arachidonic Acid to Produce N-Acylphosphatidyl-ethanolamine (NAPE), Which Is Converted by a Phospholipase D (PLD) in AEA; the Latter Is Inactivated by the Enzyme Fatty Acid Amide Hydrolase (FAAH). These Reactions Seem to Occur in Postsynaptic Terminal, While Catalyzer Enzymes for 2-arachidonoylglycerol (2-AG) Biosynthesis (Phospholipases C [PLC] and sn-1-selective Diacylglycerol Lipases [DAGL]) Are Peculiarly Localized in Postsynaptic Neurons. Monoacylglycerol Lipase (MAGL), Which Catalyzes 2-AG Inactivation, Is Instead Located in Presynaptic Neurons, Supporting a Possible Role as a Retrograde Messenger on Presynaptic CB1 Receptors for This Compound.