Dahlmann Burkhardt
Institut für Biochemie, Charité-Universitätsmedizin-Berlin, Monbijoustr, 2, 10117 Berlin, Germany.
BMC Biochem. 2007 Nov 22;8 Suppl 1(Suppl 1):S3. doi: 10.1186/1471-2091-8-S1-S3.
A functional ubiquitin proteasome system is essential for all eukaryotic cells and therefore any alteration to its components has potential pathological consequences. Though the exact underlying mechanism is unclear, an age-related decrease in proteasome activity weakens cellular capacity to remove oxidatively modified proteins and favours the development of neurodegenerative and cardiac diseases. Up-regulation of proteasome activity is characteristic of muscle wasting conditions including sepsis, cachexia and uraemia, but may not be rate limiting. Meanwhile, enhanced presence of immunoproteasomes in aging brain and muscle tissue could reflect a persistent inflammatory defence and anti-stress mechanism, whereas in cancer cells, their down-regulation reflects a means by which to escape immune surveillance. Hence, induction of apoptosis by synthetic proteasome inhibitors is a potential treatment strategy for cancer, whereas for other diseases such as neurodegeneration, the use of proteasome-activating or -modulating compounds could be more effective. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
功能性泛素蛋白酶体系统对所有真核细胞都至关重要，因此其任何组成部分的改变都可能产生潜在的病理后果。尽管确切的潜在机制尚不清楚，但蛋白酶体活性随年龄增长而下降会削弱细胞清除氧化修饰蛋白的能力，并有利于神经退行性疾病和心脏疾病的发展。蛋白酶体活性上调是包括败血症、恶病质和尿毒症在内的肌肉萎缩状况的特征，但可能不是限速因素。同时，免疫蛋白酶体在衰老的大脑和肌肉组织中增加，可能反映了一种持续的炎症防御和抗应激机制，而在癌细胞中，它们的下调反映了一种逃避免疫监视的方式。因此，合成蛋白酶体抑制剂诱导细胞凋亡是一种潜在的癌症治疗策略，而对于其他疾病，如神经退行性疾病，使用蛋白酶体激活或调节化合物可能更有效。出版历史：重新发表自Current BioData的靶向蛋白质数据库（TPdb；http://www.targetedproteinsdb.com）。
