Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun 130021, China.
Stroke Center, Department of Neurology, the First Hospital of Jilin University, Changchun 130021, China.
Biomed Pharmacother. 2024 Oct;179:117311. doi: 10.1016/j.biopha.2024.117311. Epub 2024 Aug 24.
The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).
中枢神经系统(CNS)疾病的潜在机制仍不清楚,这限制了有效治疗策略的发展。值得注意的是,细胞衰老,即体外培养的成纤维细胞中观察到的一种生物学现象,是影响大脑微环境稳态的关键内在机制,并导致 CNS 疾病的发生和进展。细胞衰老已在体外和体内建立的疾病模型以及 CNS 疾病患者的体液或组织成分中观察到。这些发现强调了细胞衰老作为预防和治疗 CNS 疾病的有希望的靶点。因此,针对衰老细胞的新兴新型疗法在与衰老相关疾病的临床前和临床研究中表现出了有希望的治疗效果。这些创新疗法有可能延缓脑细胞丢失和功能变化,改善 CNS 疾病的预后,并为患者提供替代治疗。在本研究中,我们检查了该领域的相关进展,特别是关注针对大脑中衰老细胞的靶向治疗,以治疗慢性神经退行性疾病(如阿尔茨海默病、帕金森病和多发性硬化症)和急性神经创伤性损伤(如缺血性中风、脊髓损伤和创伤性脑损伤)。