神经退行性病

    Endocannabinoid metabolism and Alzheimer’s disease
  • Figure 1|Cartoon illustrating potential signaling pathways mediating enhanced 2-AG signaling in alleviation of neuropathology and improvement of cognitive function in AD.  

    Alzheimer’s disease (AD) is the most common cause of dementia in the elderly.  Unfortunately, there are no effective therapies currently available for prevention and treatment of AD. As it is clear now, the etiology of AD is multifactorial and complex. This means that development of AD is linked to multiple mechanisms or signaling pathways and that a single-target therapy for AD is likely insufficient to achieve therapeutic goals. Therefore, an ideal therapy for AD should be able to modify the disease through multiple signaling pathways.  2-Arachidonoylglycerol (2-AG) is an endogenous cannabinoid (endocannabinoid) displaying anti-inflammatory and neuroprotective properties, while its metabolites are arachidonic acid (AA) and AA-derived prostaglandins and leukotrienes, which are proinflammatory and neurotoxic (Figure 1). The results from recent studies show that restraining 2-AG degradation reduces neuroinflammation, Aβ formation and tau phosphorylation, maintains the synaptic integrity, and improves long-term synaptic plasticity and cognitive function in mouse models of AD (Chen et al., 2012; Piro et al., 2012; Zhang et al., 2014; Zhang and Chen, 2018; Hashem et al., 2021). These beneficial effects produced by inhibition of 2-AG metabolism result likely from enhanced 2-AG signaling and concurrently decreased eicosanoid levels as 2-AG and eicosanoids mediate multiple signaling pathways (Figure 1), suggesting that limiting 2-AG metabolism in the brain would be an ideal therapy for AD. 


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  • 发布日期: 2022-03-10  浏览: 383
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