Artículo
A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson's disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies
Cukierman, Daphne Schneider; Pinheiro, Ana Beatriz; Castiñeiras-Filho, Sergio L.P.; da Silva, Anastácia Sá P.; Miotto, Marco César
; De Falco, Anna; de P. Ribeiro, Thales; Maisonette, Silvia; da Cunha, Alessandra L.M.C.; Hauser-Davis, Rachel A.; Fernandez, Claudio Oscar
; Aucélio, Ricardo Q.; Outeiro, Tiago F.; Pereira, Marcos D.; Fernandez, Claudio Oscar
; Rey, Nicolás A.
Fecha de publicación:
05/2017
Editorial:
Elsevier Science Inc
Revista:
Journal of Inorganic Biochemistry
ISSN:
0162-0134
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential ‘Metal-Protein Attenuating Compound’ for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200 mg kg− 1. INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24 h after intraperitoneal administration. After 48 h, brain clearance is complete. INHHQ is able to disrupt, in vitro, anomalous copper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compound is non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization. INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well.
Palabras clave:
Copper
,
Metal Hypothesis
,
Mpac
,
Parkinson'S Disease
,
Wistar Rats
,
Α-Synuclein
Archivos asociados
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Identificadores
Colecciones
Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos(IBR)
Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Citación
Cukierman, Daphne Schneider; Pinheiro, Ana Beatriz; Castiñeiras-Filho, Sergio L.P.; da Silva, Anastácia Sá P.; Miotto, Marco César; et al.; A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson's disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies; Elsevier Science Inc; Journal of Inorganic Biochemistry; 170; 5-2017; 160-168
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