Asoh Sadamitsu, Ohta Shigeo
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki-city, Kanagawa 211-8533, Japan.
Adv Drug Deliv Rev. 2008 Mar 1;60(4-5):499-516. doi: 10.1016/j.addr.2007.09.011. Epub 2007 Nov 13.
Millions of unnecessary cells are removed from our body everyday by apoptosis to ensure our survivals. Apoptosis is a highly coordinated process. Failure in apoptotic regulation results in disease. A large number of studies have demonstrated that accelerated apoptosis is involved in degenerative diseases, ischemic injuries, immunodeficiency and infertility. These studies have also revealed the molecular mechanisms of apoptosis signal transduction to provide therapeutic targets. On the other hand, protein transduction technology has been developed to deliver full-length proteins to various tissues including the brain. So far, many studies have shown that in vivo delivery of therapeutic proteins/peptides, including anti-apoptotic proteins, an anti-oxidant enzyme, a neuroprotectant, enzymes involved in purine or tyrosine metabolism, caspase inhibitors, c-Jun N-terminal kinase inhibitors and an NF-kappaB inhibitor, by protein transduction technology mitigates various diseases in animal models.
每天,数以百万计不必要的细胞通过细胞凋亡从我们的身体中被清除,以确保我们的生存。细胞凋亡是一个高度协调的过程。凋亡调节失败会导致疾病。大量研究表明,加速的细胞凋亡与退行性疾病、缺血性损伤、免疫缺陷和不孕症有关。这些研究还揭示了细胞凋亡信号转导的分子机制,以提供治疗靶点。另一方面,蛋白质转导技术已被开发用于将全长蛋白质递送至包括大脑在内的各种组织。到目前为止,许多研究表明,通过蛋白质转导技术在体内递送治疗性蛋白质/肽,包括抗凋亡蛋白、抗氧化酶、神经保护剂、参与嘌呤或酪氨酸代谢的酶、半胱天冬酶抑制剂、c-Jun氨基末端激酶抑制剂和NF-κB抑制剂,可减轻动物模型中的各种疾病。