title: Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease.
abstract: OBJECTIVE
  Adults who develop type 2 diabetes (T2D) at later stages are at a higher risk of developing Alzheimer's disease (AD). Pharmacological agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors that increase the levels of glucagon-like peptide-1 (GLP-1) and ameliorate T2D have also become promising candidates as disease-modifying agents in the treatment of AD. The present study investigates the efficacy of vildagliptin, a DPP-4 inhibitor in a streptozotocin (STZ)-induced rat model of AD.
  
  
  METHODS
  Three months following the induction of AD by intracerebral injection of STZ, animals were orally administered with vildagliptin (2.5, 5 and 10 mg/kg) for 30 days. Dose-dependent and time-course effects of vildagliptin on memory retention were investigated during the course of treatment. Following treatment, the animals were sacrificed, and brain tissues were used to evaluate the effects of vildagliptin on hippocampal and cortical GLP-1 levels, amyloid beta (Aβ) burden, tau phosphorylation and inflammatory markers.
  
  
  RESULTS
  The results reveal a time-dependent improvement in memory retention and a dose-dependent attenuation of Aβ, tau phosphorylation and inflammatory markers and increased GLP-1 levels.
  
  
  CONCLUSIONS
  These robust therapeutic effects of vildagliptin demonstrate a unique mechanism for Aβ and tau clearance and reverse the cognitive deficits and pathology observed in AD.
authors.affiliation: Department of Pharmacognosy, JSS College of Pharmacy, Udhagamandalam, Tamilnadu, India.
authors.forename: Jayasankar
authors.initials: J
authors.lastname: Kosaraju
authors.forename: Vishakantha
authors.initials: V
authors.lastname: Murthy
authors.forename: Rizwan Basha
authors.initials: RB
authors.lastname: Khatwal
authors.forename: Anil
authors.initials: A
authors.lastname: Dubala
authors.forename: Santhivardhan
authors.initials: S
authors.lastname: Chinni
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Muthureddy Nataraj
authors.forename: Duraiswamy
authors.initials: D
authors.lastname: Basavan
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000032:analysis; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009570:Nitriles / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000077597:Vildagliptin; D016875:tau Proteins / Q000032:analysis
chemical_list: D016229:Amyloid beta-Peptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D009570:Nitriles; D011759:Pyrrolidines; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D013311:Streptozocin; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane
keywords: amyloid beta; dipeptidyl peptidase-4; glucagon-like peptide-1; tau; type 2 diabetes