Basu_2024_Ageing.Neurodegener.Dis_4_12

Parkinson's disease (PD) is a prevalent degenerative movement disorder largely attributed to the dysfunction of dopamine transmission in the basal ganglia. However, the role of the endocannabinoid (eCB) system (ECS) in PD pathology and symptomatology is often overlooked in discussions. Recent research, including our own, has identified multiple homozygous loss-of-function variants in diacylglycerol lipase beta (DAGLB), an enzyme involved in the synthesis of 2-arachidonoyl-glycerol (2-AG) - the most abundant eCB in the brain - in individuals with early-onset autosomal recessive Parkinsonism. These genetic findings strongly link eCB deficiency with the etiopathogenesis of PD. Exploring the roles of DAGLB and 2-AG signaling in PD and dopamine transmission could provide a new perspective on PD treatments, focusing on the function of the ECS and the pathophysiological implications of its disruption.