An enquiry to the role of CB1 receptors in neurodegeneration

Neurodegenerative disorders are debilitating conditions that impair patient quality of life and that represent heavy social-economic burdens to society. Whereas the root of some of these brain illnesses lies in autosomal inheritance, the origin of most of these neuropathologies is scantly understood. Similarly, the cellular and mo-lecular substrates explaining the progressive loss of brain functions remains to be fully described too. Indeed, the study of brain neurodegeneration has resulted in a complex picture, composed of a myriad of altered processes that include broken brain bioenergetics, widespread neuroinflammation and aberrant activity of signaling pathways. In this context, several lines of research have shown that the endocannabinoid system (ECS) and its main signaling hub, the type-1 cannabinoid (CB1) receptor are altered in diverse neurodegenerative disorders. However, some of these data are conflictive or poorly described. In this review, we summarize the findings about the alterations in ECS and CB1 receptors signaling in three representative brain illnesses, the Alzheimer's, Parkinson's and Huntington's diseases, and we discuss the relevance of these studies in understanding neuro-degeneration development and progression, with a special focus on astrocyte function. Noteworthy, the analysis of ECS defects in neurodegeneration warrant much more studies, as our conceptual understanding of ECS function has evolved quickly in the last years, which now include glia cells and the subcellular-specific CB1 receptors signaling as critical players of brain functions.

Automated summary

Neurodegenerative disorders are debilitating conditions with unclear origins and mechanisms. However, studies have shown that the endocannabinoid system (ECS) and its main receptor, the type-1 cannabinoid (CB1) receptor, are altered in diseases such as Alzheimer's, Parkinson's, and Huntington's. This review summarizes the findings and highlights the importance of understanding the role of ECS and CB1 receptor signaling in neurodegeneration, specifically in astrocyte function. More research is required to fully comprehend the impact of ECS defects in these disorders.