Mechanism and prevention of neurotoxicity caused by beta-amyloid peptides: relation to Alzheimer's disease

Brain Research
Barbara J BlanchardV M Ingram

Abstract

In Alzheimer's disease, neurotoxic beta-amyloid peptides cause a deleterious influx of calcium ions into neurons. This increase in [Ca2+]int is expected to trigger intracellular events that eventually cause cell dysfunction and cell death. We find that the aggregated beta-amyloid peptide beta AP25-35 opens irreversibly a Ca(2+)-carrying channel, as does aggregated beta AP1-42. The opening of this channel is unaffected by DL-AP5, but it is blocked by Mg2+, CNQX and DNQX, suggesting a non-NMDA channel. External calcium enters and cytosolic calcium levels rise several-fold, as measured by fura-2 ratiometric analysis. Our findings illustrate a very early molecular event in the neurotoxicity of Alzheimer's disease. To combat the neurotoxic effect of aggregated beta-amyloid peptides, we have devised a series of very short antagonistic peptides. Using a combinatorial library of hexapeptides made from D-amino acids, we have selected peptides by their ability to complex with the tagged beta-amyloid peptide beta AP25-35. Certain of these so-called 'decoy peptides', as well as some modified decoy peptides, are able to abolish the calcium influx caused by aggregated, probably fibrillar, beta-amyloid peptides beta AP25-35 and beta AP1-42.

References

Sep 1, 1992·Neurobiology of Aging·C W CotmanA Copani
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·N W KowallB A Yankner
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·N ArispeE Rojas
Dec 1, 1994·Biophysical Journal·S R DurellH B Pollard
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D P YounkinD Pleasure
Dec 1, 1994·The Journal of Cell Biology·K S Kosik
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Lorenzo, B A Yankner
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·N ArispeH B Pollard
Aug 1, 1995·Neuroendocrinology·D R Giovannucci, E L Stuenkel

❮ Previous
Next ❯

Citations

Jan 13, 2004·Neurotoxicity Research·Andréa C Paula-LimaSérgio T Ferreira
Jul 1, 2000·Journal of the American Aging Association·D Harman
Jun 11, 2002·Biochemical and Biophysical Research Communications·Barbara J BlanchardVernon M Ingram
Jun 11, 2002·Biochemical and Biophysical Research Communications·Barbara J BlanchardVernon M Ingram
Nov 17, 2009·The Journal of Biological Chemistry·Jorge ParodiLuis G Aguayo
Oct 7, 2004·Journal of the American College of Nutrition·Mildred S SeeligBella T Altura
Jul 13, 2000·Protein Science : a Publication of the Protein Society·M AltmanS Zhang
Sep 30, 2004·Proceedings of the National Academy of Sciences of the United States of America·Tinsley H Davis
Sep 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Barbara J BlanchardVernon M Ingram
Sep 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yuan LuoPeter Butko
Sep 7, 2006·Experimental Brain Research·Patricia Souza dos SantosPaulo Cesar de Carvalho-Alves
Feb 4, 2012·The Journal of Physical Chemistry. B·Olujide O Olubiyi, Birgit Strodel
Mar 11, 2008·Journal of Molecular Biology·Alexandra Esteras-ChopoManuela López de la Paz
Feb 29, 2008·Dalton Transactions : an International Journal of Inorganic Chemistry·Arvi Rauk
Feb 6, 2010·Journal of Neurochemistry·Scott E Counts, Elliott J Mufson
Sep 1, 2007·The Journal of Biological Chemistry·Thomas J Nelson, Daniel L Alkon
Mar 13, 2003·Chemical Reviews·Douglas A HortonMark L Smythe
Jun 23, 2004·Molecular and Cellular Neurosciences·Woojin LeeInhee Mook-Jung
Oct 23, 2004·The Journal of Organic Chemistry·Young Soo KimKim D Janda

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.