Abstract
With the increase of life expectancy, neurodegenerative disorders are becoming not only a health but also a social burden worldwide. However, due to the multitude of pathophysiological disease states, current treatments fail to meet the desired outcomes. Therefore, there is a need for new therapeutic strategies focusing on more integrated, personalized and effective approaches. The prospect of using neural stem cells (NSC) as regenerative therapies is very promising, however several issues still need to be addressed. In particular, the potential actions of pharmacological agents used to modulate NSC activity are highly relevant. With the ongoing discussion of cannabinoid usage for medical purposes and reports drawing attention to the effects of cannabinoids on NSC regulation, there is an enormous, and yet, uncovered potential for cannabinoids as treatment options for several neurological disorders, specifically when combined with stem cell therapy. In this manuscript, we review in detail how cannabinoids act as potent regulators of NSC biology and their potential to modulate several neurogenic features in the context of pathophysiology.
Highlights
The development of a multicellular organism can be compared to a choreographed dance of cellular and molecular interactions involving cell reorganization during precise stages
The resulting N-arachidonoyl-phosphatidyl ethanolamine (NArPE) is cleaved by a calcium-dependent NAPE (N-acyl-phosphatidylethanolamine)-specific phospholipase D (NAPE-PLD), releasing the AEA from membrane lipids. This eCB is hydrolyzed into arachidonic acid and ethanolamine by fatty acid amide hydrolase (FAAH) [31]. 2-AG, on the other hand, can be synthesized by two different metabolic pathways: via the cleavage of diacylglycerol by diacylglycerol lipase (DAGL), where diacylglycerol is released from membrane phospholipids by phospholipase C (PLC) or via the action of phospholipase A1 (PLA1), releasing an sn-1 lysophospholipid from membrane phospholipids, which is cleaved by lyso-PLC in order to generate 2-AG
In recent years there has been a growing increase in the number of reports highlighting the effects of cannabinoids on neural stem cells (NSC) regulation [180,210,231]
Summary
The development of a multicellular organism can be compared to a choreographed dance of cellular and molecular interactions involving cell reorganization during precise stages. A “neurogenic niche” can be defined as a complex microenvironment that supports NSCs and their progeny, helping to determine whether NSCs remain dormant or divide, by providing signals that guide early stages of proliferation or differentiation. One of these signals has been shown to come through the action of endocannabinoids (eCBs), mainly via activation of cannabinoid receptors type 1 and 2 (CB1R and CB2R). Increasing data has been showing an important role for cannabinoids in NSC modulation, which might allow combining their wide range of actions with the multitude of applications that stem cells offer. We provide a summary of cannabinoid actions and its effects in NSC modulation both in development and in the adult brain, highlighting the role of cannabinoids in pathophysiology and as therapeutic agents for neuroregeneration
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