Title:Interplay Between Endocannabinoid System and Neurodegeneration:
Focus on Polypharmacology
Volume: 29
Issue: 28
关键词:
内源性大麻素系统，神经退行性疾病，多靶点药物，阿尔茨海默病，帕金森病，大麻素受体，FAAH，MAGL。
摘要: Pharmacological treatment of complex pathologies, such as neurodegenerative
diseases still represents a major challenge, due to the networked pathways involved in
their onset and progression that may require equally complex therapeutic approaches.
Polypharmacology, based on the simultaneous modulation of multiple targets involved in
the disease, may offer the potential to increase effectiveness and reduce the drawbacks related
to the use of drug combinations. Clearly, this approach requires both the knowledge
of the systems responsible for disease development and the discovery of new attractive
targets to be exploited to design a multitarget drug. Over the last years, an ever increasing
interest has focused on the endocannabinoid system, implicated in the modulation of several
physiological functions, among which neuroinflammation, a crucial process for most
neurodegenerative diseases. In this respect, the cannabinoid receptor subtype 2 represents
a promising therapeutic target, being overexpressed in microglia cells and thus involved
in neuroinflammation. The indirect modulation of this system through the inhibition of
the main enzymes responsible for endocannabinoids metabolism, namely fatty acid amide
hydrolase and monoacylglycerol lipase, may also significantly affect neurodegenerative
processes. The aim of this review is to give an overview of the opportunities posed by the
endocannabinoid system for neurodegenerative diseases management, mainly focusing on
the potential for a multitarget strategy.
