Yuan Huiqi, Zhu Bin, Li Cao, Zhao Zhigang
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Front Cell Neurosci. 2023 Jun 2;17:1191609. doi: 10.3389/fncel.2023.1191609. eCollection 2023.
Ceramide, a bioactive sphingolipid, serves as an important second messenger in cell signal transduction. Under stressful conditions, it can be generated from synthesis, sphingomyelin hydrolysis, and/or the salvage pathway. The brain is rich in lipids, and abnormal lipid levels are associated with a variety of brain disorders. Cerebrovascular diseases, which are mainly caused by abnormal cerebral blood flow and secondary neurological injury, are the leading causes of death and disability worldwide. There is a growing body of evidence for a close connection between elevated ceramide levels and cerebrovascular diseases, especially stroke and cerebral small vessel disease (CSVD). The increased ceramide has broad effects on different types of brain cells, including endothelial cells, microglia, and neurons. Therefore, strategies that reduce ceramide synthesis, such as modifying sphingomyelinase activity or the rate-limiting enzyme of the synthesis pathway, serine palmitoyltransferase, may represent novel and promising therapeutic approaches to prevent or treat cerebrovascular injury-related diseases.
神经酰胺是一种生物活性鞘脂,在细胞信号转导中作为重要的第二信使。在应激条件下,它可以通过合成、鞘磷脂水解和/或补救途径产生。大脑富含脂质,脂质水平异常与多种脑部疾病有关。脑血管疾病主要由脑血流异常和继发性神经损伤引起,是全球范围内死亡和残疾的主要原因。越来越多的证据表明神经酰胺水平升高与脑血管疾病密切相关,尤其是中风和脑小血管疾病(CSVD)。升高的神经酰胺对不同类型的脑细胞有广泛影响,包括内皮细胞、小胶质细胞和神经元。因此,减少神经酰胺合成的策略,如调节鞘磷脂酶活性或合成途径的限速酶丝氨酸棕榈酰转移酶,可能代表预防或治疗脑血管损伤相关疾病的新颖且有前景的治疗方法。