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Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer's disease.
Inestrosa, Nibaldo C; Carvajal, Francisco J; Zolezzi, Juan M; Tapia-Rojas, Cheril; Serrano, Felipe; Karmelic, Daniel; Toledo, Enrique M; Toro, Andrés; Toro, Jessica; Santos, Manuel J.
Afiliação
  • Inestrosa NC; Centro de Envejecimiento y Regeneración (CARE), Santiago, Chile Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. ninestrosa@bio.puc.cl
J Alzheimers Dis ; 33(4): 941-59, 2013.
Article em En | MEDLINE | ID: mdl-23109558
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, accumulation of the amyloid-ß peptide (Aß), increase of oxidative stress, and synaptic alterations. The scavenging of reactive oxygen species through their matrix enzyme catalase is one of the most recognized functions of peroxisomes. The induction of peroxisome proliferation is attained through different mechanisms by a set of structurally diverse molecules called peroxisome proliferators. In the present work, a double transgenic mouse model of AD that co-expresses a mutant human amyloid-ß protein precursor (AßPPswe) and presenilin 1 without exon 9 (PS1dE9) was utilized in order to assess the effect of peroxisomal proliferation on Aß neurotoxicity in vivo. Mice were tested for spatial memory and their brains analyzed by cytochemical, electrophysiological, and biochemical methods. We report here that peroxisomal proliferation significantly reduces (i) memory impairment, found in this model of AD; (ii) Aß burden and plaque-associated acetylcholinesterase activity; (iii) neuroinflammation, measured by the extent of astrogliosis and microgliosis; and (iv) the decrease in postsynaptic proteins, while promoting synaptic plasticity in the form of long-term potentiation. We concluded that peroxisomal proliferation reduces various AD neuropathological markers and peroxisome proliferators may be considered as potential therapeutic agents against the disease.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Química Encefálica / Proliferadores de Peroxissomos / Doença de Alzheimer / Transtornos da Memória / Degeneração Neural Limite: Animals / Humans / Male Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Química Encefálica / Proliferadores de Peroxissomos / Doença de Alzheimer / Transtornos da Memória / Degeneração Neural Limite: Animals / Humans / Male Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Chile País de publicação: Holanda