Sharma Veerta, Singh Thakur Gurjeet
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.
Metab Brain Dis. 2025 May 21;40(5):209. doi: 10.1007/s11011-025-01636-4.
Neurodegenerative diseases (NDDs) are characterised by the progressive degeneration of neurons in the brain, resulting in impairments in memory, cognition, and motor abilities. Common pathological features include altered energy metabolism, neuroinflammation, death of neurons, aberrant protein aggregation, and synaptic dysfunction. Chitinase-3-like-1 (CHI3-L1) is an evolutionarily conserved protein involved in variety of biological processes such as neuroinflammation, tissue remodelling and angiogenesis. Elevated levels of CHI3-L1 have been detected in the cerebrospinal fluid and plasma of patients with NDDs, suggesting its involvement in disease progression. As a critical regulator of neuroinflammation, CHI3-L1 modulates the activity of astrocyte and microglia, causing the production of pro-inflammatory cytokines that worsens disease progression. In addition to its involvement in disease pathophysiology, it has emerged as a potential biomarker for the diagnosis and monitoring of neurological diseases. However, significant knowledge gaps persist regarding its molecular mechanisms, interactions with inflammatory mediators, and influence on blood-brain barrier integrity. Therefore, this review highlights the emerging role of CHI3-L1 in neurodegeneration and describes future research approaches targeted at unlocking its therapeutic potential in treating NDDs.
神经退行性疾病(NDDs)的特征是大脑中的神经元进行性退化,导致记忆、认知和运动能力受损。常见的病理特征包括能量代谢改变、神经炎症、神经元死亡、异常蛋白质聚集和突触功能障碍。几丁质酶-3样-1(CHI3-L1)是一种进化上保守的蛋白质,参与多种生物学过程,如神经炎症、组织重塑和血管生成。在NDDs患者的脑脊液和血浆中检测到CHI3-L1水平升高,表明其参与疾病进展。作为神经炎症的关键调节因子,CHI3-L1调节星形胶质细胞和小胶质细胞的活性,导致促炎细胞因子的产生,从而加剧疾病进展。除了参与疾病病理生理学外,它已成为神经疾病诊断和监测的潜在生物标志物。然而,关于其分子机制、与炎症介质的相互作用以及对血脑屏障完整性的影响,仍然存在重大的知识空白。因此,本综述强调了CHI3-L1在神经退行性变中的新作用,并描述了旨在挖掘其在治疗NDDs中治疗潜力的未来研究方法。