Intranasal Delivery of NEMO-Binding Domain Peptide Prevents Memory Loss in a Mouse Model of Alzheimer's Disease.
J Alzheimers Dis
; 47(2): 385-402, 2015.
Article
em En
| MEDLINE
| ID: mdl-26401561
ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia. Despite intense investigations, no effective therapy is available to halt its progression. We found that NF-κB was activated within the hippocampus and cortex of AD subjects and that activated forms of NF-κB negatively correlated with cognitive function monitored by Mini-Mental State Examination and global cognitive z score. Accordingly, NF-κB activation was also observed in the hippocampus of a transgenic (5XFAD) mouse model of AD. It has been shown that peptides corresponding to the NF-κB essential modifier (NEMO)-binding domain (NBD) of IκB kinase α (IKKα) or IκB kinase ß (IKKß) specifically inhibit the induction of NF-κB activation without inhibiting the basal NF-κB activity. Interestingly, after intranasal administration, wild-type NBD peptide entered into the hippocampus, reduced hippocampal activation of NF-κB, suppressed hippocampal microglial activation, lowered the burden of Aß in the hippocampus, attenuated apoptosis of hippocampal neurons, protected plasticity-related molecules, and improved memory and learning in 5XFAD mice. Mutated NBD peptide had no such protective effect, indicating the specificity of our finding. These results suggest that selective targeting of NF-κB activation by intranasal administration of NBD peptide may be of therapeutic benefit for AD patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Nootrópicos
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Doença de Alzheimer
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Hipocampo
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Transtornos da Memória
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Alzheimers Dis
Ano de publicação:
2015
Tipo de documento:
Article