Department of Brain and Learning Science, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, Nanjing, China.
Cannabis Cannabinoid Res. 2023 Jun;8(3):445-463. doi: 10.1089/can.2022.0267. Epub 2023 Feb 6.
Despite the successful introduction of combined antiretroviral therapy, the prevalence of mild to moderate forms of HIV-associated neurocognitive disorders (HAND) remains high. It has been demonstrated that neuronal injury caused by HIV is excitotoxic and inflammatory, and it correlates with neurocognitive decline in HAND. Endocannabinoid system (ECS) protects the body from excitotoxicity and neuroinflammation on demand and presents a promising therapeutic target for treating HAND. Here, we firstly discuss the potential pathogenesis of HAND. We secondly discuss the structural and functional changes in the ECS that are currently known among HAND patients. We thirdly discuss current clinical and preclinical findings concerning the neuroprotective and anti-inflammatory properties of the ECS among HAND patients. Fourth, we will discuss the interactions between the ECS and neuroendocrine systems, including the hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes under the HAND conditions. We have carried out a review of the literature using PubMed to summarize the current state of knowledge on the association between ECS and HAND. The ECS may be ideally suited for modulation of HAND pathophysiology. Direct activation of presynaptic cannabinoid receptor 1 or reduction of cannabinoid metabolism attenuates HAND excitotoxicity. Chronic neuroinflammation associated with HAND can be reduced by activating cannabinoid receptor 2 on immune cells. The sensitivity of the ECS to HIV may be enhanced by increased cannabinoid receptor expression in HAND. In addition, indirect regulation of the ECS through modulation of hormone-related receptors may be a potential strategy to influence the ECS and also alleviate the progression of HAND due to the reciprocal inhibition of the ECS by the HPA and HPG axes. Taken together, targeting the ECS may be a promising strategy to alleviate the inflammation and neurodegeneration caused by HIV-1 infection. Further studies are required to clarify the role of endocannabinoid signaling in HIV neurotoxicity. Strategies promoting endocannabinoid signaling may slow down cognitive decline of HAND are proposed.
尽管联合抗逆转录病毒疗法已成功引入，但 HIV 相关神经认知障碍（HAND）的轻度至中度形式的流行率仍然很高。已经证明，HIV 引起的神经元损伤是兴奋性毒性和炎症性的，并且与 HAND 中的神经认知下降相关。内源性大麻素系统（ECS）按需保护身体免受兴奋性毒性和神经炎症的侵害，并且是治疗 HAND 的有前途的治疗靶标。在这里，我们首先讨论 HAND 的潜在发病机制。我们其次讨论了在 HAND 患者中目前已知的 ECS 的结构和功能变化。我们第三讨论了当前关于 HAND 患者中 ECS 的神经保护和抗炎特性的临床和临床前发现。第四，我们将讨论 ECS 与神经内分泌系统之间的相互作用，包括 HAND 条件下的下丘脑-垂体-肾上腺皮质（HPA）和下丘脑-垂体-性腺（HPG）轴。我们使用 PubMed 对文献进行了综述，以总结 ECS 与 HAND 之间关联的当前知识状态。 ECS 可能非常适合调节 HAND 病理生理学。直接激活突触前大麻素受体 1 或降低大麻素代谢可减轻 HAND 的兴奋性毒性。通过激活免疫细胞上的大麻素受体 2 可以减少与 HAND 相关的慢性神经炎症。HAND 中大麻素受体表达增加可能会增强 ECS 对 HIV 的敏感性。此外，通过调节与激素相关的受体对 ECS 的间接调节可能是一种潜在的策略，通过 ECS 与 HPA 和 HPG 轴的相互抑制来影响 ECS 并减轻 HAND 的进展。 总之，针对 ECS 可能是减轻 HIV-1 感染引起的炎症和神经退行性变的有前途的策略。需要进一步的研究来阐明内源性大麻素信号在 HIV 神经毒性中的作用。提出了促进内源性大麻素信号的策略可能会减缓 HAND 的认知下降。
