Boullon Laura, Abalo Raquel, Llorente-Berzal Álvaro
Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland.
Centre for Pain Research, National University of Ireland, Galway, Ireland.
Front Pharmacol. 2021 Nov 12;12:734613. doi: 10.3389/fphar.2021.734613. eCollection 2021.
In recent years, and particularly associated with the increase of cancer patients' life expectancy, the occurrence of cancer treatment sequelae, including cognitive impairments, has received considerable attention. Chemotherapy-induced cognitive impairments (CICI) can be observed not only during pharmacological treatment of the disease but also long after cessation of this therapy. The lack of effective tools for its diagnosis together with the limited treatments currently available for alleviation of the side-effects induced by chemotherapeutic agents, demonstrates the need of a better understanding of the mechanisms underlying the pathology. This review focuses on the comprehensive appraisal of two main processes associated with the development of CICI: neuroinflammation and oxidative stress, and proposes the endogenous cannabinoid system (ECS) as a new therapeutic target against CICI. The neuroprotective role of the ECS, well described in other cognitive-related neuropathologies, seems to be able to reduce the activation of pro-inflammatory cytokines involved in the neuroinflammatory supraspinal processes underlying CICI. This review also provides evidence supporting the role of cannabinoid-based drugs in the modulation of oxidative stress processes that underpin cognitive impairments, and warrant the investigation of endocannabinoid components, still unknown, that may mediate the molecular mechanism behind this neuroprotective activity. Finally, this review points forward the urgent need of research focused on the understanding of CICI and the investigation of new therapeutic targets.
近年来,尤其是随着癌症患者预期寿命的增加,包括认知障碍在内的癌症治疗后遗症的发生受到了广泛关注。化疗引起的认知障碍(CICI)不仅在疾病的药物治疗期间可以观察到,而且在这种治疗停止后很长时间也能观察到。缺乏有效的诊断工具以及目前用于减轻化疗药物引起的副作用的治疗方法有限,这表明需要更好地了解该病理的潜在机制。本综述重点全面评估了与CICI发生相关的两个主要过程:神经炎症和氧化应激,并提出内源性大麻素系统(ECS)作为对抗CICI的新治疗靶点。ECS的神经保护作用在其他与认知相关的神经病理学中已有充分描述,似乎能够减少参与CICI潜在神经炎症脊髓上过程的促炎细胞因子的激活。本综述还提供了证据,支持基于大麻素的药物在调节导致认知障碍的氧化应激过程中的作用,并保证对仍未知的内源性大麻素成分进行研究,这些成分可能介导这种神经保护活性背后的分子机制。最后,本综述指出迫切需要开展研究,重点是了解CICI并探索新的治疗靶点。