title: Overexpression of human HSP27 protects sensory neurons from diabetes.
abstract: OBJECTIVE
  To evaluate whether augmenting neuronal protective mechanisms might slow or arrest experimental diabetic peripheral neuropathy (DPN). DPN is one of the most common neurodegenerative disorders and is rising in prevalence. How it targets sensory neurons is uncertain; the disorder is irreversible and untreatable. We explored the intrinsic protective properties of overexpressed human HSP27 on experimental DPN. HSP27 is a small pro-survival heat shock protein that also increases axonal regeneration.
  
  
  METHODS
  Experimental diabetes was superimposed on mice overexpressing a human HSP27 transgene and its impact was evaluated on epidermal innervation, behavioral tests of sensation and electrophysiological indices of DPN.
  
  
  RESULTS
  Mice that overexpress human HSP27 in their sensory and motor neurons and that were made diabetic for 6 months by streptozotocin treatment were protected from a range of neuropathic abnormalities, including loss of footpad thermal sensation, mechanical allodynia, loss of epidermal innervation, and slowing of sensory conduction velocity. The protection was selective for sensory neurons in comparison to motor neurons and at 6 months provided better protection in female than male mice. Markers of RAGE-NFκB activation were attenuated by the transgene.
  
  
  CONCLUSIONS
  The findings support the idea that diabetic polyneuropathy involves a unique, sensory-centric neurodegenerative process which can be reduced by overexpressing a single gene, an important starting point for new disease-modifying therapeutic approaches.
authors.affiliation: Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Korngut
authors.forename: C H E
authors.initials: CH
authors.lastname: Ma
authors.forename: J A
authors.initials: JA
authors.lastname: Martinez
authors.forename: C C
authors.initials: CC
authors.lastname: Toth
authors.forename: G F
authors.initials: GF
authors.lastname: Guo
authors.forename: V
authors.initials: V
authors.lastname: Singh
authors.forename: C J
authors.initials: CJ
authors.lastname: Woolf
authors.forename: D W
authors.initials: DW
authors.lastname: Zochodne
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006442:Glycated Hemoglobin / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006930:Hyperalgesia / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000235:genetics; D017288:Pain Threshold / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012867:Skin / Q000294:innervation / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology; D013997:Time Factors; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D001786:Blood Glucose; D053148:Caspase 3; D006442:Glycated Hemoglobin; D055551:HSP27 Heat-Shock Proteins; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D013311:Streptozocin; D000097782:NF-kappaB-Inducing Kinase; C498977:Mok protein, mouse