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Prosaptide exacerbates ischemia-induced behavioral deficits in vivo; an effect that does not involve mitogen-activated protein kinase activation.

Abstract
Prosaposin is a 517 amino acid membrane component and secreted protein(5,7,9) that is proteolytically cleaved to generate the four small glycoproteins; saposins A, B, C and D.(9,13,19) Prosaposin's ability to promote neurite outgrowth(31) and to protect neurons from programmed cell death(28) in vitro, as well as to rescue neurons from ischemia and other damage in vivo(11,12,15,25) implied that prosaposin was neurotrophic/neuroprotectant.(1,7,24,31) The neurotrophic sequence of prosaposin was isolated to smaller peptide fragments termed prosaptides(15,31) within the amino terminal portion of saposin C.(1,6,8,10,17,20,21,28) The proposed use of synthetic prosaptides as peripherally administered neuroprotective and/or neurotrophic therapeutic agents has stemmed from their ability to cross the blood-brain barrier,(27) as well as their reported neurotrophic activity in vitro.(15,23,31) Few studies, however, have attempted to characterize these peptides, presumably due to their reported instability following peripheral administration.(27) With the recent design of a stable 11-mer retro-inverso prosaptide,(15,31) it has become feasible to investigate the pharmacological effects of a stable version of these peptides in the validated rabbit spinal cord ischemia model that has been used extensively in the development of therapeutics to treat ischemic stroke.(4,14,16,18) Our results show not only that prosaptide was not neurotrophic/neuroprotectant in vivo, but rather it worsened ischemia-induced behavioral deficits.
AuthorsP A Lapchak, D M Araujo, D A Shackelford, J A Zivin
JournalNeuroscience (Neuroscience) Vol. 101 Issue 4 Pg. 811-4 ( 2000) ISSN: 0306-4522 [Print] United States
PMID11113331 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Nerve Growth Factors
  • prosaptide
  • Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Enzyme Activation (physiology)
  • Ischemia (psychology)
  • Mental Disorders (etiology, psychology)
  • Mitogen-Activated Protein Kinases (metabolism)
  • Nerve Growth Factors (pharmacology)
  • Rabbits
  • Spinal Cord (blood supply)

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