Intranasal Delivery Of Nemo-Binding Domain Peptide Prevents Memory Loss In A Mouse Model Of Alzheimer'S Disease
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-ÎºB was activated within the hippocampus and cortex of AD subjects and that activated forms of NF-ÎºB negatively correlated with cognitive function monitored by Mini-Mental State Examination and global cognitive z score. Accordingly, NF-ÎºB 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-ÎºB essential modifier (NEMO)-binding domain (NBD) of IÎºB kinase Î± (IKKÎ±) or IÎºB kinase Î² (IKKÎ²) specifically inhibit the induction of NF-ÎºB activation without inhibiting the basal NF-ÎºB activity. Interestingly, after intranasal administration, wild-type NBD peptide entered into the hippocampus, reduced hippocampal activation of NF-ÎºB, suppressed hippocampal microglial activation, lowered the burden of AÎ² 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-ÎºB activation by intranasal administration of NBD peptide may be of therapeutic benefit for AD patient
Journal of Alzheimer's Disease
Digital Object Identifier (DOI)
Rangasamy, Suresh B.; Corbett, Grant T.; Roy, Avik; Modi, Khushbu K.; Bennett, David A.; Mufson, Elliott J.; Ghosh, Sankar; and Pahan, Kalipada, "Intranasal Delivery Of Nemo-Binding Domain Peptide Prevents Memory Loss In A Mouse Model Of Alzheimer'S Disease" (2015). Neurobiology. 327.