Dalle-Donne Isabella, Aldini Giancarlo, Carini Marina, Colombo Roberto, Rossi Ranieri, Milzani Aldo
Department of Biology, University of Milan, Italy.
J Cell Mol Med. 2006 Apr-Jun;10(2):389-406. doi: 10.1111/j.1582-4934.2006.tb00407.x.
Carbonylation of proteins is an irreversible oxidative damage, often leading to a loss of protein function, which is considered a widespread indicator of severe oxidative damage and disease-derived protein dysfunction. Whereas moderately carbonylated proteins are degraded by the proteasomal system, heavily carbonylated proteins tend to form high-molecular-weight aggregates that are resistant to degradation and accumulate as damaged or unfolded proteins. Such aggregates of carbonylated proteins can inhibit proteasome activity. Alarge number of neurodegenerative diseases are directly associated with the accumulation of proteolysis-resistant aggregates of carbonylated proteins in tissues. Identification of specific carbonylated protein(s) functionally impaired and development of selective carbonyl blockers should lead to the definitive assessment of the causative, correlative or consequential role of protein carbonylation in disease onset and/or progression, possibly providing new therapeutic approaches.
蛋白质羰基化是一种不可逆的氧化损伤，常常导致蛋白质功能丧失，它被认为是严重氧化损伤和疾病衍生的蛋白质功能障碍的普遍指标。适度羰基化的蛋白质由蛋白酶体系统降解，而高度羰基化的蛋白质则倾向于形成高分子量聚集体，这些聚集体抗降解，并作为受损或未折叠的蛋白质积累。这种羰基化蛋白质聚集体可抑制蛋白酶体活性。大量神经退行性疾病与组织中抗蛋白水解聚集体的羰基化蛋白质积累直接相关。鉴定功能受损的特定羰基化蛋白质并开发选择性羰基阻断剂应能对蛋白质羰基化在疾病发生和/或进展中的因果、相关或后续作用进行明确评估，可能会提供新的治疗方法。
