Abstract
The Endocannabinoid System (ECS) is a well-studied system that influences a variety
of physiological activities. It is evident that the ECS plays a significant role in metabolic activities
and also has some neuroprotective properties. In this review, we emphasize several plant-derived
cannabinoids such as β-caryophyllene (BCP), Cannabichromene (CBC), Cannabigerol (CBG),
Cannabidiol (CBD), and Cannabinol (CBN), which are known to have distinctive modulation abilities
of ECS. In Alzheimer's disease (AD), the activation of ECS may provide neuroprotection by
modulating certain neuronal circuitry pathways through complex molecular cascades. The present
article also discusses the implications of cannabinoid receptors (CB1 and CB2) as well as cannabinoid
enzymes (FAAH and MAGL) modulators in AD. Specifically, CBR1 or CB2R modulations
result in reduced inflammatory cytokines such as IL-2 and IL-6, as well as a reduction in
microglial activation, which contribute to an inflammatory response in neurons. Furthermore, naturally
occurring cannabinoid metabolic enzymes (FAAH and MAGL) inhibit the NLRP3 inflammasome
complex, which may offer significant neuroprotection. In this review, we explored the
multi-targeted neuroprotective properties of phytocannabinoids and their possible modulations,
which could offer significant benefits in limiting AD.
Keywords:
Phytocannabinoids, Alzheimer’s disease, cannabinoid receptors, neuroinflammation, NLRP3 inflammasome proteins, CB1 and CB2.
Graphical Abstract
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