Antognelli Cinzia, Perrelli Andrea, Armeni Tatiana, Nicola Talesa Vincenzo, Retta Saverio Francesco
Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy.
Department of Clinical and Biological Sciences, University of Torino, Orbassano, 10043 Torino, Italy.
Antioxidants (Basel). 2020 Feb 1;9(2):124. doi: 10.3390/antiox9020124.
Dicarbonyl stress is a dysfunctional state consisting in the abnormal accumulation of reactive α-oxaldehydes leading to increased protein modification. In cells, post-translational changes can also occur through S-glutathionylation, a highly conserved oxidative post-translational modification consisting of the formation of a mixed disulfide between glutathione and a protein cysteine residue. This review recapitulates the main findings supporting a role for dicarbonyl stress and S-glutathionylation in the pathogenesis of cerebrovascular diseases, with specific emphasis on cerebral cavernous malformations (CCM), a vascular disease of proven genetic origin that may give rise to various clinical signs and symptoms at any age, including recurrent headaches, seizures, focal neurological deficits, and intracerebral hemorrhage. A possible interplay between dicarbonyl stress and S-glutathionylation in CCM is also discussed.
二羰基应激是一种功能失调状态,表现为反应性α-氧代醛异常积累,导致蛋白质修饰增加。在细胞中,翻译后修饰也可通过S-谷胱甘肽化发生,这是一种高度保守的氧化翻译后修饰,由谷胱甘肽与蛋白质半胱氨酸残基之间形成混合二硫键组成。本综述总结了支持二羰基应激和S-谷胱甘肽化在脑血管疾病发病机制中作用的主要研究结果,特别强调了脑海绵状血管畸形(CCM),这是一种已证实有遗传起源的血管疾病,可在任何年龄引发各种临床症状和体征,包括反复发作的头痛、癫痫、局灶性神经功能缺损和脑出血。还讨论了CCM中二羰基应激和S-谷胱甘肽化之间可能的相互作用。