Modulation of the Cannabinoid System: A New Perspective for the Treatment of the Alzheimer’s Disease
Author:
Talarico Giuseppina1, Trebbastoni Alessandro1, Bruno Giuseppe1, de Lena Carlo1
Affiliation:
1. Department of Human Neuroscience, Sapienza, University of Rome, Rome, Italy
Abstract
The pathogenesis of Alzheimer’s disease (AD) is somewhat complex and has yet to be
fully understood. As the effectiveness of the therapy currently available for AD has proved to be
limited, the need for new drugs has become increasingly urgent. The modulation of the endogenous
cannabinoid system (ECBS) is one of the potential therapeutic approaches that is attracting a growing
amount of interest. The ECBS consists of endogenous compounds and receptors. The receptors
CB1 and CB2 have already been well characterized: CB1 receptors, which are abundant in the
brain, particularly in the hippocampus, basal ganglia and cerebellum, regulate memory function and
cognition. It has been suggested that the activation of CB1 receptors reduces intracellular Ca concentrations,
inhibits glutamate release and enhances neurotrophin expression and neurogenesis. CB2
receptors are expressed, though to a lesser extent, in the central nervous system, particularly in the
microglia and immune system cells involved in the release of cytokines. CB2 receptors have been
shown to be upregulated in neuritic plaque-associated microglia in the hippocampus and entorhinal
cortex of patients, which suggests that these receptors play a role in the inflammatory pathology of
AD. The role of the ECBS in AD is supported by cellular and animal models. By contrast, few
clinical studies designed to investigate therapies aimed at reducing behaviour disturbances, especially
night-time agitation, eating behaviour and aggressiveness, have yielded positive results. In
this review, we will describe how the manipulation of the ECBS offers a potential approach to the
treatment of AD.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology (medical),Psychiatry and Mental health,Clinical Neurology,Neurology,Pharmacology,General Medicine
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