Abstract：
It has been more than a decade since the discovery of a novel class of phosphatase, the Pleckstrin Homology (PH) domain Leucine-rich repeat Protein Phosphatases (PHLPP). Over time, they have been recognized as crucial regulators of various cellular processes, such as memory formation, cellular survival and proliferation, maintenance of circadian rhythm, and others, with any deregulation in their expression or cellular localization causing havoc in any cellular system. With the ever-growing number of downstream substrates across multiple tissue systems, a web is emerging wherein the central point is PHLPP. A slight nick in the normal signaling cascade of the two isoforms of PHLPP, namely PHLPP1 and PHLPP2, has been recently found to invoke a variety of neurological disorders including Alzheimer\'s disease, epileptic seizures, Parkinson\'s disease, and others, in the neuronal system. Improper regulation of the two isoforms has also been associated with various disease pathologies such as diabetes, cardiovascular disorders, cancer, musculoskeletal disorders, etc. In this review, we have summarized all the current knowledge about PHLPP1 (PHLPP1α and PHLPP1β) and PHLPP2 and their emerging roles in regulating various neuronal signaling pathways to pave the way for a better understanding of the complexities. This would in turn aid in providing context for the development of possible future therapeutic strategies.
摘要：
自从发现一类新的磷酸酶以来，已经有十多年了，Pleckstrin同源性(PH)结构域富含亮氨酸的重复蛋白磷酸酶(PHLPP)。随着时间的推移,它们被认为是各种细胞过程的关键调节剂，比如记忆形成，细胞存活和增殖，维持昼夜节律，和其他人,它们的表达或细胞定位的任何失调都会在任何细胞系统中造成严重破坏。随着跨多个组织系统的下游基质数量的不断增加，出现网,其中中心点是PHLPP。在PHLPP两种同工型的正常信号级联中略有缺口，即PHLPP1和PHLPP2，最近已发现引起各种神经系统疾病，包括阿尔茨海默病，癫痫发作,帕金森病,和其他人,在神经元系统中。两种亚型的不当调节也与各种疾病病理有关，例如糖尿病，心血管疾病,癌症,肌肉骨骼疾病，等。在这次审查中,我们总结了目前有关PHLPP1（PHLPP1α和PHLPP1β）和PHLPP2的所有知识，以及它们在调节各种神经元信号通路中的新兴作用，为更好地理解复杂性铺平道路。这反过来将有助于为开发可能的未来治疗策略提供背景。
