Data/hora: 05/06/2024 16:22:45

Provedor de dados: 	48	
País: 	Chile	
Título: 	Histidines 13 and 14 in the A&amp;#946; sequence are targets for inhibition of Alzheimer's disease A&amp;#946; ion channel and cytotoxicity	
Autores: 	DÍAZ,JUAN CARLOS; LINNEHAN,JOHN; POLLARD,HARVEY; ARISPE,NELSON.	
Data: 	2006-01-01	
Ano: 	2006	
Palavras-chave: 	Alzheimer's disease; Beta amyloid; Ion channel blockers; Peptides; Histidine; Toxicity.	
Resumo: 	The fact that Alzheimer's beta amyloid (A&amp;#946;) peptides forms cation channels in lipid bilayers was discovered during the course of our experiments in the laboratory of "Guayo" Rojas at NIH in Bethesda, Maryland (USA). Recently, we found that the A&amp;#946; ion channel could be blocked selectively with small peptides that copy the amino acid sequence of the predicted mouth region of the A&amp;#946; channel pore. We now have searched for the essential amino acid residues required for this blocking effect by mutations. We found that the ability of peptides to block A&amp;#946; channel activity could be lost by replacement of histidines 13 and 14 by alanine or lysine. The amino acid substitution also resulted in the loss of the capacity of the peptides to protect cells from A&amp;#946; cytotoxicity. These data thus contribute to the definition of the region of the A&amp;#946; sequence that participates in the formation of the channel pore. Additionally, these data support the hypothesis that the ion channel activity of Ab contributes significantly to the cytotoxic properties of A&amp;#946;. These data also emphasize the potential value in using inhibition of A&amp;#946; ion channel activity as an end point for Alzheimer's disease drug discovery.	
Tipo: 	Journal article	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000300007	
Editor: 	Sociedad de Biología de Chile	
Formato: 	text/html	
Fonte: 	Biological Research  v.39 n.3 2006