Efficiency of histidine-associating compounds for blocking the alzheimer's Abeta channel activity and cytotoxicity.

Biophysical Journal
Nelson ArispeMichael Flora

Abstract

The opening of the Alzheimer's Abeta channel permits the flux of calcium into the cell, thus critically disturbing intracellular ion homeostasis. Peptide segments that include the characteristic histidine (His) diad, His(13) and His(14), efficiently block the Abeta channel activity, blocking Abeta cytotoxicity. We hypothesize that the vicinal His-His peptides coordinate with the rings of His in the mouth of the pore, thus blocking the flow of calcium ions through the channel, with consequent blocking of Abeta cytotoxicity. To test this hypothesis, we studied Abeta ion channel activity and cytotoxicity after the addition of compounds that are known to have His association capacity, such as Ni(2+), imidazole, His, and a series of His-related compounds. All compounds were effective at blocking both Abeta channel and preventing Abeta cytotoxicity. The efficiency of protection of His-related compounds was correlated with the number of imidazole side chains in the blocker compounds. These data reinforce the premise that His residues within the Abeta channel sequence are in the pathway of ion flow. Additionally, the data confirm the contribution of the Abeta channel to the cytotoxicity of exogenous Abeta.

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Dec 1, 1994·Biophysical Journal·S R DurellH B Pollard
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·D T LooC W Cotman
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·N ArispeH B Pollard
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·N ArispeE Rojas
Jun 5, 1998·The Journal of Biological Chemistry·S K RheeR Lal
Jun 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Y J ZhuR Lal
Oct 29, 2000·European Journal of Biochemistry·D S YangP E Fraser
Feb 24, 2001·Annals of the New York Academy of Sciences·B A Yankner
Sep 25, 2001·Cellular and Molecular Neurobiology·J I KourieP Farrelly
Jul 19, 2002·Nature·Hilal A LashuelPeter T Lansbury
Jul 20, 2002·Peptides·Bruce L KaganMeng-Chin Lin
Oct 31, 2002·Journal of the American Chemical Society·Steve ScheinerJayasree Pattanayak
Nov 5, 2002·Nature Reviews. Neuroscience·Frank M LaFerla
Jun 20, 2003·Journal of Proteome Research·Rajasri BhattacharyyaPinak Chakrabarti
Mar 12, 2004·The Journal of Membrane Biology·N Arispe
Feb 22, 2005·The Journal of Biological Chemistry·Angelo DemuroCharles G Glabe
Jul 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arjan QuistRatnesh Lal
May 11, 2007·Biochimica Et Biophysica Acta·Nelson ArispeOlga Simakova
Jun 8, 2007·Biochimica Et Biophysica Acta·Ratnesh LalArjan P Quist
Jul 17, 2007·Progress in Biophysics and Molecular Biology·Pinak Chakrabarti, Rajasri Bhattacharyya
Jan 10, 2008·Trends in Biochemical Sciences·Hyunbum JangRuth Nussinov

❮ Previous
Next ❯

Citations

Feb 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Juan Carlos DiazHarvey B Pollard
May 7, 2011·International Journal of Alzheimer's Disease·Masahiro KawaharaYutaka Sadakane
May 1, 2009·Expert Review of Neurotherapeutics·Masahiro KawaharaYutaka Sadakane
Nov 20, 2013·Metallomics : Integrated Biometal Science·Masahiro KawaharaYutaka Sadakane
Jun 26, 2014·Chembiochem : a European Journal of Chemical Biology·Marie C HeffernThomas J Meade
Sep 29, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sebastian K T S WärmländerAstrid Gräslund
Jul 9, 2010·The Journal of Physical Chemistry. B·Hyunbum JangRuth Nussinov
Jul 3, 2021·International Journal of Molecular Sciences·Xiaoyu ZhangHuiling Gao
Sep 6, 2013·Langmuir : the ACS Journal of Surfaces and Colloids·Arjun ThapaEva Y Chi

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis