Endocannabinoids in Alzheimer's Disease
Alzheimer's disease (AD), the major cause of dementia, is a chronic neurodegenerative disorder. Although our understanding of the cellular and molecular events involved in the pathophysiology of the disease has greatly advanced, few effective therapies had been introduced into the clinic. The characterization of the cannabinoid system has been defined during the last few years and cannabinoid-based therapies are beginning to be recognized for the treatment of different diseases. According to recent evidence, cannabinoid receptors are localized to senile plaques in AD brain, in particular in activated microglial cell clusters. On the other hand, cortical CB1 positive neurons are lost and CB1 receptor expression and functioning are markedly decreased in the neurologic disorder. Furthermore, in AD models, in vivo cannabinoids prevent the cognitive impairment, while reducing the loss of neuronal markers and of markers of gliosis. The beneficial effects of cannabinoids in preventing neurotoxicity induced by β-amyloid (Aβ) may rely on the anti-inflammatory properties of cannabinoids, given that they reduce the effects Aβ on microglial cells and on astrocytes, as judged by in vitro experiments, and can be brought about by both cannabinoid receptor-dependent and -independent mechanisms. These findings may set the basis for the use of these compounds, that combine both anti-inflammatory and neuroprotective actions, as a therapeutic approach for AD.
KeywordsMicroglial Cell Microglial Activation Senile Plaque Fatty Acid Amide Hydrolase Nitrite Generation
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