PTEN as a therapeutic target in motor neuron diseases (ALS/SMA)
European Journal of Molecular & Clinical Medicine,
2015, Volume 2, Issue 2, Pages -
AbstractThe tumor suppressor protein Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN) is a member of the protein tyrosine phosphatase family that can negatively regulate the serine/threonine kinase Akt to exert its tumour suppressor function. In addition to its normal functions such as neuronal migration and neuronal size control, PTEN protein is involved in pathological processes surrounding neuronal injury such as those associated with brain ischemia, neurological and mental disorders. It has been shown that modulation of the PTEN/mTOR pathway promotes axon regeneration in the adult CNS. We have previously shown that down-regulating the expression of PTEN protects against ischaemic neuronal death in vitro and in vivo (Ning et al. 2014). Recently, we showed that PTEN knockdown via siRNA increases motor neuron survival in Amyotrophic lateral sclerosis (ALS) (Kirby et al. 2011) in vitro and spinal muscular atrophy (SMA) in vivo (Ning et al. 2010, Little et al., unpublished). Our preliminary data show that the PTEN inhibitor, bpV, promotes cell survival in NSC34 G93A motor neuronal cell line.
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