5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Neuroprotective effects of the amylin analogue pramlintide on Alzheimer's disease pathogenesis and cognition.

      Neurobiology of Aging
      Aged, Aged, 80 and over, Alzheimer Disease, drug therapy, metabolism, psychology, Animals, Cells, Cultured, Cognition, drug effects, Cyclin-Dependent Kinase 5, Disease Models, Animal, Female, Hippocampus, Humans, Hypoglycemic Agents, pharmacology, therapeutic use, Islet Amyloid Polypeptide, Male, Memory, Mice, Middle Aged, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Neurons, Neuroprotective Agents, Oxidative Stress, Receptors, Islet Amyloid Polypeptide, Synapsins

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Amylin is a metabolic peptide hormone that is co-secreted with insulin from beta cells in the pancreas and activates many of the downstream targets of insulin. To investigate the relationship between this hormone and Alzheimer's disease (AD), we measured plasma human amylin levels in 206 subjects with AD, 64 subjects with mild cognitive impairment, and 111 subjects with no cognitive impairment and found significantly lower amylin levels among subjects with AD and mild cognitive impairment compared with the cognitively intact subjects. To investigate mechanisms underlying amylin's effects in the brain, we administered chronic infusions of the amylin analog pramlintide in the senescence-accelerated prone mouse, a mouse model of sporadic AD. Pramlintide administration improved performance in the novel object recognition task, a validated test of memory and cognition. The pramlintide-treated mice had increased expression of the synaptic marker synapsin I and the kinase cyclin-dependent kinase-5 in the hippocampus, as well as decreased oxidative stress and inflammatory markers in the hippocampus. A dose-dependent increase in cyclin-dependent kinase-5 and activation of extracellular-signal-regulated-kinases 1/2 by pramlintide treatment in vitro was also present indicating functionality of the amylin receptor in neurons. Together these results suggest that amylin analogs have neuroprotective properties and might be of therapeutic benefit in AD. Copyright © 2014 Elsevier Inc. All rights reserved.

          Related collections

          Author and article information

          Comments

          Comment on this article