title: Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder.
abstract: BACKGROUND
  Compelling evidence has shown that diabetic metabolic disorder plays a critical role in the pathogenesis of Alzheimer's disease, including increased expression of β-amyloid protein (Aβ) and tau protein. Evidence has supported that minocycline, a tetracycline derivative, protects against neuroinflammation induced by neurodegenerative disorders or cerebral ischemia. This study has evaluated minocycline influence on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the brain of diabetic rats to clarify neuroprotection by minocycline under diabetic metabolic disorder.
  
  
  METHODS
  An animal model of diabetes was established by high fat diet and intraperitoneal injection of streptozocin. In this study, we investigated the effect of minocycline on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of diabetic rats via immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  These results showed that minocycline decreased expression of Aβ protein and lowered the phosphorylation of tau protein, and retarded the proinflammatory cytokines, but not amyloid precursor protein.
  
  
  CONCLUSIONS
  On the basis of the finding that minocycline had no influence on amyloid precursor protein and beta-site amyloid precursor protein cleaving enzyme 1 which determines the speed of Aβ generation, the decreases in Aβ production and tau hyperphosphorylation by minocycline are through inhibiting neuroinflammation, which contributes to Aβ production and tau hyperphosphorylation. Minocycline may also lower the self-perpetuating cycle between neuroinflammation and the pathogenesis of tau and Aβ to act as a neuroprotector. Therefore, the ability of minocycline to modulate inflammatory reactions may be of great importance in the selection of neuroprotective agents, especially in chronic conditions like diabetes and Alzheimer's disease.
authors: Department of Neurology, the Lu'an Affiliated Hospital of Anhui Medical University, Lu'an People's Hospital, Lu'an, Anhui Province, People's Republic of China. c0909@hotmail.com
authors: Zhiyou
authors: Z
authors: Cai
authors: Yong
authors: Y
authors: Yan
authors: Yonglong
authors: Y
authors: Wang
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D048909:Diabetes Complications / Q000150:complications* / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D008911:Minocycline / Q000276:immunology / Q000494:pharmacology*; D023421:Models, Animal; D020078:Neurogenic Inflammation / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000900:Anti-Bacterial Agents; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D008911:Minocycline
keywords: diabetes mellitus; minocycline; tau protein; β-amyloid protein
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