英语翻译

The clinical and therapeutic implications of mTOR are widespread and continue to expand.Abnormal mTOR activity, leading to excessive cellular growth and proliferation, has been implicated in the pathophysiology of numerous human cancers, including both sporadic,isolated tumors of specific organs and multiorgan, genetic tumor syndromes (Guertin and Sabatini, 2007). In many of these cases, specific mutations of some component of the mTOR signaling pathway have been documented, resulting in hyperactivation of mTOR or its downstream effectors. Besides cancer, dysregulation of mTOR has also been implicated in a number of other diseases, involving metabolic or environmental derangements, such as diabetes, obesity, cardiovascular disease, and neurodegenerative disorders (Tsang et al.,2007). From a translational standpoint, the potential role of mTOR in the pathophysiology ofthese various disorders has immediate therapeutic implications, as a number of clinically available drugs exist that inhibit mTOR, including the prototype, rapamycin. Thus, rapamycin and other mTOR inhibitors are already being tested in clinical trials for various cancers and other diseases (Dancey, 2006; Tsang et al., 2007).

Overall, mTOR appears to serve as a master switch responding to different physiological
and pathological stimuli to maintain homeostasis by regulating cellular growth,
proliferation, and survival. mTOR is increasingly recognized to be involved in a large
spectrum of physiological functions under normal conditions and to be dysregulated in a diverse group of diseases. mTOR inhibitors, such as rapamycin, are being considered or are already in clinical trials for a number of these diseases. Based on the physiological and pathophysiological properties of mTOR, it is reasonable to hypothesize that mTOR
signaling could be involved in mechanisms of epileptogenesis. In the remainder of this
review, evidence for the role of mTOR in epileptogenesis and the potential utility of mTOR inhibitors as anti-epileptogenic agents will be analyzed in different types of epilepsies, starting with the genetic epilepsy, Tuberous Sclerosis Complex, and other tumor- or cortical malformation-associated epilepsies, and extending to more common, acquired epilepsies.

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