Endocannabinoid system as a potential target for neurodegenerative diseases

Abstract

Neurodegenerative diseases (ND) represent a critical social and economic problem worldwide and are becoming highly prevalent because of the increasing average age of the population. ND is characterized by exacerbated neural death which leads to motor, cognitive or behavioural diss representing an important cause of disability and mortality. Both its development and maintenance have been investigated over the last decades. In most of them, there is a chronic neuroinflammatory state establishment commonly associated with pathological protein aggregation, as evidenced in AD, PD and HD. This neuroinflammatory state is recognized by microglial hyperactivation, inflammatory cytokines storm and neural death, compromising the neurological environment. Accordingly, in the last decades, intensive efforts have been put into investigating the main pathways involved in its development and new pharmacological approaches to management it. Since the ’80s, when cannabinoid receptors (CB1R and CB2R) were discovered, the endocannabinoid system modulation has been investigated in many diseases context in order to the millenary medicinal use of cannabis. Nowadays, have already been described the different roles played by components that make up it, such as antitumoral, regulation of neurotransmission in different brain regions, inflammatory modulation, and regulation of glial cells. In this context, this work aimed to provide a summarized translational review of the most recent studies about the involvement of the ECS in NDs development and maintenance, as well as a therapeutic target.