New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain

Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand the mechanism...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2017-03, Vol.93 (6), p.1296-1313
Main Authors: Feldman, Eva L., Nave, Klaus-Armin, Jensen, Troels S., Bennett, David L.H.
Format: Article
Language:English
Subjects:
Animals
axon-glia crosstalk
Axons - physiology
Bioenergetics
Bioinformatics
Biotechnology
Brain research
Diabetes
Diabetes mellitus
Diabetic Neuropathies - metabolism
Diabetic Neuropathies - physiopathology
Diabetic neuropathy
Energy Metabolism - physiology
Epidemics
Humans
Models, Neurological
Nervous system
Neuralgia - metabolism
Neuralgia - physiopathology
Neurons
Pain
Pathogenesis
Patients
Paving
Peripheral nervous system
Peripheral Nervous System - physiopathology
Peripheral neuropathy
pre-diabetes
Rodents
Schwann cell
Schwann Cells - metabolism
Schwann Cells - physiology
type 1 diabetes
type 2 diabetes
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Summary:Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our understanding of DN pathogenesis are paving the way for critical mechanism-based therapy development. Nearly a quarter of a billion people worldwide have diabetic neuropathy. However, despite high morbidity, there are no disease-modifying therapies for the disorder. Four international experts review new experimental advances in the field with an eye toward future mechanism-based therapies.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2017.02.005