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Is PTEN hyperactivity behind poor regeneration in diabetic neuropathy?

Aviva M. Tolkovsky
DOI: http://dx.doi.org/10.1093/brain/awu048 977-978 First published online: 19 March 2014

Neuropathy is a troublesome complication of diabetes mellitus that commonly affects the sensory and autonomic nervous systems. Impaired nerve conduction and axonopathy lead to pain and/or paraesthesia followed by sensory loss. There is no effective treatment for diabetic neuropathy, in part because its mechanisms are poorly understood. Research has focused on correcting the changes induced by hyperglycaemia, such as oxidative stress, glycation of macromolecules, and mitochondrial dysfunction (Tomlinson and Gardiner, 2008). Neuroprotective strategies that target neurons, Schwann cells, and nerve blood supply have also been suggested (Calcutt et al., 2008) but none have been successful (Apfel, 2002; Ropper et al., 2009). However, in this issue of Brain, Douglas Zochodne and colleagues present evidence that inhibition of the phosphatase PTEN (phosphatase and tensin homolog) can produce functional improvements in a mouse model of diabetic neuropathy (Singh et al., 2014).

A frequent consequence of diabetic neuropathy, in addition to nerve degeneration, is the failure of axons to regenerate after injury. Recent studies of axon regeneration in the CNS have focused on the phosphatase PTEN. PTEN dephosphorylates the signalling lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3) at position three. PIP3 mediates growth factor receptor signalling (including that of insulin) through activation of PI3-kinase at the plasma membrane. Activation of PTEN thus reduces activity in critical signalling pathways …

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