title: 17-AAG improves cognitive process and increases heat shock protein response in a model lesion with Aβ25-35.
abstract: Molecular chaperones, or heat shock proteins (HSP), have been implicated in numerous neurodegenerative disorders characterized by the accumulation of protein aggregates, such as Alzheimer disease. The agglomeration of insoluble structures of Aβ is thought to be responsible for neuronal death, which in turn leads to the loss of cognitive functions. Recent findings have shown that the induction of HSP decreases the level of abnormal protein aggregates, as well as demonstrating that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an analogue of geldanamycin (GA), increases Aβ clearance through the induction of molecular chaperones in cell culture. In light of this discovery that HSP overexpression can be neuroprotective, the search for a way to pharmacologically induce the overexpression of HSP and other associated chaperones may lead to a promising approach for the treatment of neurodegenerative diseases. The aim of our study was to evaluate both the effect of 17-AAG on the cognitive process and the HSP response in rats injected with Aβ25-35 into the CA1 of the hippocampus. The results show that the injection of Aβ caused a significant increase in the expression of the HSP involved in the regulation of cellular proteostasis. While the HSP did not reverse excitotoxic damage, given that experimental subjects showed learning and memory deficits, the administration of 17-AAG prior to the injection of Aβ25-35 did show an improvement in the behavioral assessment that correlated with the upregulation of HSP70 in subjects injured with Aβ. Overall, our data shows that the pharmacological induction of HSP using 17-AAG may be an alternative treatment of neurodegenerative diseases.
authors.affiliation: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico; Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F. 04510, Mexico. Electronic address: gaezra@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Ortega
authors.affiliation: Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, México D.F. 14269, Mexico. Electronic address: dol_grape@yahoo.com.mx.
authors.forename: Minerva
authors.initials: M
authors.lastname: Calvillo
authors.affiliation: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico. Electronic address: felix.luna@fcquim.buap.mx.
authors.forename: Félix
authors.initials: F
authors.lastname: Luna
authors.affiliation: Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, México D.F. 14269, Mexico. Electronic address: fseverian@yahoo.com.
authors.forename: Francisca
authors.initials: F
authors.lastname: Pérez-Severiano
authors.affiliation: Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, México D.F. 14269, Mexico. Electronic address: ruomnd@yahoo.com.mx.
authors.forename: Moisés
authors.initials: M
authors.lastname: Rubio-Osornio
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F. 04510, Mexico. Electronic address: jorge_guevara@icloud.com.
authors.forename: Jorge
authors.initials: J
authors.lastname: Guevara
authors.affiliation: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico. Electronic address: dlimonperezdeleon@yahoo.com.mx.
authors.forename: Ilhuicamina Daniel
authors.initials: ID
authors.lastname: Limón
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D016227:Benzoquinones / Q000627:therapeutic use*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D047029:Lactams, Macrocyclic / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018697:Nootropic Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018697:Nootropic Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C112765:tanespimycin
keywords: 17-AAG; Alzheimer’s disease; Amyloid beta 25–35; Heat shock protein; Hippocampus; Memory impairment