Axonal growth and functional recovery following SCI are limited, because of poor innate regenerative capacity of adult central nervous system neurons and hostile injury environment comprising inflammation, myelin- associated inhibitors, glial scar components and compromised blood supply. As one of the major intrinsic impediments to axonal growth, PTEN is expressed in neurons and regenerating axons and plays a vital role in controlling the regeneration of corticospinal neurons via downregulating cytoplasmic mammalian Target of Rapamycin (mTOR) activity.
This mTOR pathway is intensely inhibited in axotomized adult neurons, restricting protein synthesis to sustain axonal growth.
This unique activity makes PTEN a major homeostatic regulator and tumor suppressor protein, which function is absent or defective in a wide variety of tumors as a result of somatic alterations. The important role of the PI3K/AKT/mTOR signaling pathway in cell growth, regeneration and survival supports the rationale for the therapeutic targeting of PTEN.
Among the suggested PTEN inhibition-based therapeutic targets are nerve growth and regeneration after injury or damage, treatment of cardiac ischemia/reperfusion and associated disease, wound repair, and infertility.