Abstract：
Intracellular signal transduction in response to growth factor receptor activation is a fundamental process during the regeneration of the nervous system. In this context, intracellular inhibitors of neuronal growth factor signaling have become of great interest in the recent years. Among them are the prominent signal transduction regulators Sprouty (SPRY) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which interfere with major signaling pathways such as extracellular signal-regulated kinase (ERK) or phosphoinositide 3-kinase (PI3K)/Akt in neurons and glial cells. Furthermore, SPRY and PTEN are themselves tightly regulated by ubiquitin ligases such as c-casitas b-lineage lymphoma (c-CBL) or neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) and by different microRNAs (miRs) including miR-21 and miR-222. SPRY, PTEN and their intracellular regulators play an important role in the developing and the lesioned adult central and peripheral nervous system. This review will focus on the effects of SPRY and PTEN as well as their regulators in various experimental models of axonal regeneration in vitro and in vivo. Targeting these signal transduction regulators in the nervous system holds great promise for the treatment of neurological injuries in the future.
摘要：
响应生长因子受体激活的细胞内信号转导是神经系统再生过程中的基本过程。在这种情况下，近年来，神经元生长因子信号传导的细胞内抑制剂引起了人们的极大兴趣。其中有突出的信号转导调节因子Sprouty(SPRY)和10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN),干扰神经元和神经胶质细胞中的主要信号通路，如细胞外信号调节激酶（ERK）或磷酸肌醇3-激酶（PI3K）/Akt。此外，SPRY和PTEN本身受泛素连接酶如c-casitasb-谱系淋巴瘤(c-CBL)或神经前体细胞表达的发育下调蛋白4(NEDD4)以及不同的microRNA(miR)(包括miR-21和miR-222)紧密调节。SPRY,PTEN及其细胞内调节因子在成人中枢神经系统和周围神经系统的发育和病变中起着重要作用。本文将重点介绍SPRY和PTEN及其调节剂在体外和体内轴突再生的各种实验模型中的作用。在神经系统中靶向这些信号转导调节因子对于将来治疗神经系统损伤具有很大的希望。
