Journal
NEUROBIOLOGY OF AGING
Volume 32, Issue 8, Pages 1420-1434Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2009.08.008
Keywords
Alzheimer's disease; Neural progenitor cells; Ciliary neurotrophic factor; CNTFR alpha; Leukemia inhibitory factor; LIFR; Learning and memory disorders; Neural proliferation and differentiation; Neurogenesis
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Funding
- New York State Office of Mental Retardation and Developmental Disabilities
- EBEWE Neuro Pharma, Unterach, Austria
- T.L.L. Temple Foundation
- Alzheimer Association, Chicago, IL
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Pharmacological enhancement of hippocampal neurogenesis is a therapeutic approach for improvement of cognition in learning and memory disorders such as Alzheimer's disease. Here we report the development of an 11-mer peptide that we designed based on a biologically active region of the ciliary neurotrophic factor. This peptide, Peptide 6, induced proliferation and increased survival and maturation of neural progenitor cells into neurons in the dentate gyrus of normal adult C57BL6 mice . Furthermore, Peptide 6 increased the MAP2 and synaptophysin immunoreactivity in the denate gyrus. Thirty-day treatment of the mice with a slow release bolus of the peptide implanted subcutaneously improved reference memory of the mice in Morris water maze. Peptide 6 has a plasma half life of over 6 h, is blood-brain barrier permeable, and acts by competitively inhibiting the leukemia inhibitory factor signaling. The fact that Peptide 6 is both neurogenic and neurotrophic and that this peptide is effective when given peripherally, demonstrates its potential for prevention and treatment of learning and memory disorders. (C) 2009 Elsevier Inc. All rights reserved.
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