The Interplay between Cannabinoid Receptors and Microglia in the Pathophysiology of Alzheimer's Disease

Alzheimer's disease (AD) is characterized by massive neuronal death, brain atrophy, and loss of neurons and synapses, which all lead to a progressive cognitive decline. Neuroinflammation has been recently identified as one of the main causes of AD progression, and microglia cells are considered to have a central role in this process. Growing evidence suggests that cannabinoids may be used as preventive treatment for AD. An altered expression of the endocannabinoids (eCBs) and their receptors (CBRs) is reported in several neurodegenerative disorders, including AD. Moreover, the modulation of CBRs demonstrated neuroprotective effects in reducing aggregated protein deposition, suggesting the therapeutic potential of natural and synthetic CBR ligands in the treatment of neurodegenerative proteinopathies. Here, we review the current knowledge regarding the involvement of CBRs in the modulation of microglia activation phenotypes, highlighting the role of neuroinflammation in the pathogenesis of neurodegenerative diseases, like AD. We also provide an overview of recently developed candidate drugs targeting CBRs that may afford a new innovative strategy for the treatment and management of AD.

Automated summary

Alzheimer's disease (AD) is characterized by neuronal death, brain atrophy, and cognitive decline. Neuroinflammation, with microglia as key players, has been identified as a major cause of AD progression. Cannabinoids show potential as a preventive treatment for AD, with altered expression of endocannabinoids and their receptors reported in neurodegenerative disorders including AD. Modulation of cannabinoid receptors has been shown to have neuroprotective effects in reducing protein deposition, suggesting their therapeutic potential for neurodegenerative diseases. This review provides an overview of the involvement of cannabinoid receptors in microglia activation and highlights the role of neuroinflammation in AD pathogenesis. It also discusses recently developed candidate drugs targeting cannabinoid receptors as an innovative strategy for AD treatment and management.