Glycosaminoglycan C3 protects against AF64A-induced cholinotoxicity in a dose-dependent and time-dependent manner

Brain Research
Michael RoseIsrael Hanin

Abstract

Several studies revealed that proteoglycans (PGs) and glycosaminoglycans (GAGs) play a pivotal role in the pathogenesis of Alzheimer's disease (AD). PGs have affinity to amyloid beta (Abeta) and protect it against proteolysis, and the consequent aggregation is the cause of neurotoxicity. This effect is believed to be attenuated by GAGs. Moreover, a low-molecular-weight GAG C3 derived from unfractionated heparin has been reported to protect against Abeta-induced tau-2 immunoreactivity and cholinergic damage induced by a cholinotoxin, AF64A, in rat. However, the optimal dose and the timeframe of administration of C3 are still unknown. In our studies, we revealed the concentration-dependent and time-dependent effects of C3 on AF64A-induced cholinergic lesion in rat. C3 was administered orally in 5, 10, and 25 mg/kg/day concentration, 7 days before and/or 7 days after intracerebroventricular (i.c.v.) AF64A administration. Our results have shown that 25 mg/kg/day C3 effectively protects against AF64A-generated cholinotoxicity if administered both 7 days before and 7 days after the AF64A injection. In contrast to these findings, administration of 5 or 10 mg/kg/day C3 or 25 mg/kg/day C3, given 7 days before or 7 days after stereotaxic...Continue Reading

References

Sep 1, 1976·Brain : a Journal of Neurology·D M BowenA N Davison
Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J RogersP Ward
Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·S A FrautschyG M Cole
Jan 1, 1989·Progress in Neuro-psychopharmacology & Biological Psychiatry·L ContiA Postiglione
Jun 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·C M WischikA Klug
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
Oct 1, 1986·Physiology & Behavior·J P Kroon, A L Riley
Mar 1, 1995·Neurodegeneration : a Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration·D R HowlettG W Roberts
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Lorenzo, B A Yankner
Feb 15, 1993·Archives of Biochemistry and Biophysics·D L MillerK Iqbal
May 29, 2002·Thrombosis Research·Qing MaJawed Fareed
Jun 14, 2002·Thrombosis Research·Qing MaJawed Fareed

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