Lin Kanheng, Stiles Jacob, Tambo Willians, Ajmal Erum, Piao Quanyu, Powell Keren, Li Chunyan
Translational Brain Research Laboratory, The Feinstein Institutes for Medical Research, Manhasset, NY, USA; Emory University, Atlanta, GA, USA.
Translational Brain Research Laboratory, The Feinstein Institutes for Medical Research, Manhasset, NY, USA; The College of William & Mary, Williamsburg, VA, USA.
Life Sci. 2024 Dec 15;359:123177. doi: 10.1016/j.lfs.2024.123177. Epub 2024 Oct 30.
Calcitonin gene-related peptide (CGRP) is a pluripotent neuropeptide crucial for maintaining vascular homeostasis, yet its full therapeutic potential remains incompletely exploited. Within the brain, CGRP demonstrates a distinct bimodal effect, contributing to neuroprotection in ischemic conditions while inducing neuronal sensitization and inflammation in non-ischemic settings. Despite extensive research on CGRP, the absence of a definitive determinant for this observed dichotomy has limited its potential for therapeutic applications in the brain. This review examines the effects of CGRP in both physiological and pathological conditions, aiming to identify a unifying factor that could enhance its therapeutic applicability.
This comprehensive literature review analyzes the molecular pathways associated with CGRP and the specific cellular responses observed in these contexts. Additionally, the review investigates the psychological implications of CGRP in relation to cerebral perfusion levels, aiming to elucidate its underlying factors.
Reviewing the literature reveals that, elevated levels of CGRP in non-ischemic conditions exert detrimental effects on brain function, while they confer protective effects in the context of ischemia. These encompass anti-oxidative, anti-inflammatory, anti-apoptotic, and angiogenic properties, along with behavioral normalization. Current findings indicate promising therapeutic avenues for CGRP beyond the acute phases of cerebral injury, extending to neurodegenerative and psychological disorders associated with cerebral hypoperfusion, as well as chronic recovery following acute cerebral injuries.
Improved understanding of CGRP's bimodal properties, alongside advancements in CGRP delivery methodologies and brain ischemia detection technologies, paves the way for realizing its untapped potential and broad therapeutic benefits in diverse pathological conditions.
降钙素基因相关肽（CGRP）是一种多能神经肽，对维持血管稳态至关重要，但其全部治疗潜力仍未得到充分开发。在大脑中，CGRP表现出明显的双峰效应，在缺血条件下有助于神经保护，而在非缺血环境中则诱导神经元致敏和炎症。尽管对CGRP进行了广泛研究，但对于这种观察到的二分法缺乏明确的决定因素，限制了其在大脑治疗应用中的潜力。本综述探讨了CGRP在生理和病理条件下的作用，旨在确定一个可以增强其治疗适用性的统一因素。
这篇全面的文献综述分析了与CGRP相关的分子途径以及在这些情况下观察到的特定细胞反应。此外，该综述调查了CGRP与脑灌注水平相关的心理影响，旨在阐明其潜在因素。
回顾文献发现，在非缺血条件下CGRP水平升高对脑功能产生有害影响，而在缺血情况下则具有保护作用。这些作用包括抗氧化、抗炎、抗凋亡和血管生成特性，以及行为正常化。目前的研究结果表明，CGRP在脑损伤急性期之外具有广阔的治疗前景，可扩展到与脑灌注不足相关的神经退行性疾病和心理障碍，以及急性脑损伤后的慢性恢复。
对CGRP双峰特性的更好理解，以及CGRP递送方法和脑缺血检测技术的进步，为在各种病理条件下实现其未开发的潜力和广泛的治疗益处铺平了道路。
