Galve-Roperh Ismael, Aguado Tania, Palazuelos Javier, Guzmán Manuel
Department of Biochemistry and Molecular Biology I, School of Biology, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Complutense University, 28040 Madrid, Spain.
Curr Pharm Des. 2008;14(23):2279-88. doi: 10.2174/138161208785740117.
Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival. Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases. Nonetheless, some studies have reported that cannabinoids can also exert neurotoxic actions. Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage. Coupling of neuronal CB(1) receptors to cell survival routes such as the phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase pathways may contribute to cannabinoid neuroprotective action. These pro-survival signals occur, at least in part, by the cross-talk between CB(1) receptors and growth factor tyrosine kinase receptors. Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation. Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.
内源性大麻素作为逆行信使，通过经由突触前CB(1)大麻素受体抑制神经递质释放，调节许多突触的功能。此外，内源性大麻素系统参与神经元存活的调控。因此，已表明CB(1)受体激活可保护神经元免受急性脑损伤以及神经炎症性疾病和神经退行性疾病的侵害。尽管如此，一些研究报告称大麻素也可产生神经毒性作用。大麻素的神经保护活性依赖于对谷氨酸能神经传递的抑制以及其他各种机制，并且大脑在受损时会过量产生内源性大麻素这一观察结果也支持了这一点。神经元CB(1)受体与细胞存活途径（如磷脂酰肌醇3激酶/蛋白激酶B和细胞外信号调节激酶途径）的偶联可能有助于大麻素的神经保护作用。这些促存活信号至少部分是通过CB(1)受体与生长因子酪氨酸激酶受体之间的相互作用而产生的。除了促进神经保护作用外，内源性大麻素系统在控制神经祖细胞的神经发生中也被认为发挥作用。此外，胶质细胞上CB(2)大麻素受体的激活也可能通过限制神经炎症的程度参与神经保护。总之，这些发现支持内源性大麻素构成一类新的脂质介质家族，它们在神经元存活的调控中作为指导性信号发挥作用。
