Caruso Giuseppe, Di Pietro Lucia, Cardaci Vincenzo, Maugeri Salvatore, Caraci Filippo
Department of Drug and Health Sciences, University of Catania, Catania, Italy.
Unit of Neuropharmacology and Translational Neurosciences, Oasi Research Institute-IRCCS, Troina, Italy.
Curr Res Pharmacol Drug Discov. 2023 Mar 7;4:100153. doi: 10.1016/j.crphar.2023.100153. eCollection 2023.
Carnosine is a naturally occurring endogenous dipeptide composed by the ligation of β-alanine and L-histidine performed particularly by tissues with an increased oxidative metabolism such as muscles and brain. In the last 50 years different studies have assessed the role and function of carnosine through numerous , , and clinical studies, demonstrating the multimodal mechanism of action of this dipeptide that includes anti-aggregant, antioxidant, and anti-inflammatory activities. In particular its activity has been investigated in experimental models of cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and neurodegenerative disorders, such as cerebral ischemia and Alzheimer's disease (AD). In the present review, we examined the protective role that carnosine could exert in the context of T2DM, CVD, and AD, which show common pathogenic mechanisms including oxidative stress, inflammation, and aggregation phenomena. Carnosine's pharmacodynamic profile is multimodal and combines the systemic anti-inflammatory and antioxidant activities with its anti-aggregant and neuroprotective efficacy in the central nervous system. This enlarged pharmacological activity opens a new path to explore the therapeutic potential of carnosine in all the three diseases, and in particular in patients with T2DM, who often show a history of CVD and also have an increased risk to develop mild cognitive impairment and AD.
肌肽是一种天然存在的内源性二肽,由β-丙氨酸和L-组氨酸连接而成,在氧化代谢增加的组织如肌肉和大脑中尤为常见。在过去的50年里,不同的研究通过大量的实验、观察和临床研究评估了肌肽的作用和功能,证明了这种二肽的多模式作用机制,包括抗聚集、抗氧化和抗炎活性。特别是在心血管疾病(CVD)、2型糖尿病(T2DM)和神经退行性疾病如脑缺血和阿尔茨海默病(AD)的实验模型中研究了其活性。在本综述中,我们研究了肌肽在T2DM、CVD和AD背景下可能发挥的保护作用,这些疾病表现出包括氧化应激、炎症和聚集现象在内的共同致病机制。肌肽的药效学特征是多模式的,将全身抗炎和抗氧化活性与其在中枢神经系统中的抗聚集和神经保护功效相结合。这种扩大的药理活性为探索肌肽在所有这三种疾病中的治疗潜力开辟了一条新途径,特别是在T2DM患者中,他们通常有CVD病史,并且发生轻度认知障碍和AD的风险也增加。