Neuropep-1 ameliorates learning and memory deficits in an Alzheimer's disease mouse model, increases brain-derived neurotrophic factor expression in the brain, and causes reduction of amyloid beta plaques.
Neurobiol Aging
; 35(5): 990-1001, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24268884
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid beta (Aß) deposits, hyperphosphorylated tau deposition, and cognitive dysfunction. Abnormalities in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in learning and memory formation, have been reported in the brains of AD patients. A BDNF modulating peptide (Neuropep-1) was previously identified by positional-scanning synthetic peptide combinatorial library. Here we examine the neuroprotective effects of Neuropep-1 on several in vitro neurotoxic insults, and triple-transgenic AD mouse model (3xTg-AD). Neuropep-1 protects cultured neurons against oligomeric Aß1-42, 1-methyl-4-phenylpyridinium, and glutamate-induced neuronal cell death. Neuropep-1 injection also significantly rescues the spatial learning and memory deficits of 3xTg-AD mice compared with vehicle-treated control group. Neuropep-1 treatment markedly increases hippocampal and cortical BDNF levels. Furthermore, we found that Neuropep-1-injected 3xTg-AD mice exhibit dramatically reduced Aß plaque deposition and Aß levels without affecting tau pathology. Neuropep-1 treatment does not alter the expression or activity of full-length amyloid precursor protein, α-, ß-, or γ-secretase, but levels of insulin degrading enzyme, an Aß degrading enzyme, were increased. These findings suggest Neuropep-1 may be a therapeutic candidate for the treatment of AD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Encéfalo
/
Peptídeos beta-Amiloides
/
Fármacos Neuroprotetores
/
Fator Neurotrófico Derivado do Encéfalo
/
Placa Amiloide
/
Doença de Alzheimer
/
Aprendizagem
/
Memória
/
Neurônios
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2014
Tipo de documento:
Article