| Authors |
Kobayashi M, Zochodne DW
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| Submitted By |
Douglas Zochodne on 4/2/2018 |
| Status |
Published |
| Journal |
Journal of diabetes investigation |
| Year |
2018 |
| Date Published |
3/1/2018 |
| Volume : Pages |
Not Specified : Not Specified |
| PubMed Reference |
29533535 |
| Abstract |
Diabetic polyneuropathy (DPN) continues to be generally considered as a
"microvascular" complication of diabetes mellitus alongside nephropathy and
retinopathy. The microvascular hypothesis, however, may be tempered by the
concept that diabetes directly targets dorsal root ganglion sensory neurons.
This neuron specific concept, supported by accumulating evidence, might account
for important features of DPN, such as its early sensory neuron degeneration.
Diabetic sensory neurons develop neuronal atrophy alongside a series of mRNA
changes related to declines in structural proteins, increases in heat shock
protein (HSP), increases in the receptor for advanced glycation endproducts
(RAGE), declines in growth factor signaling and other changes. Insulin is
recognized as a potent neurotrophic factor, and insulin ligation enhances
neurite outgrowth through activation of the PI3K-Akt pathway within sensory
neurons and attenuates phenotypic features of experimental DPN. Several
interventions, including as glucagon-like peptide-1 (GLP-1) agonism, phosphatase
and tensin homolog (PTEN) inhibition, and HSP overexpression, to activate growth
signals in sensory neurons, prevent or reverse neuropathic abnormalities in
experimental DPN. Diabetic sensory neurons display a unique pattern of microRNA
alterations, a key element of mRNA silencing. For example, let-7i is widely
expressed in sensory neurons, supports their growth, and is depleted in
experimental DPN; its replenishment improves features of DPN models. Finally,
impairment of pre-mRNA splicing in diabetic sensory neurons including abnormal
nuclear RNA metabolism and structure with loss of SMN proteins, a neuron
survival molecule, and overexpression of CWC22, a splicing factor, offer further
novel insights. This review addresses these new aspects of DPN sensory
neurodegeneration. This article is protected by copyright. All rights reserved.
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