KChIP3 promotes Alzheimer's disease by impairing long-term potentiation and memory
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1150916 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR30337620_1.fastq.gz | Fastqsanger.gz | |||
| SRR30337620_2.fastq.gz | Fastqsanger.gz | |||
| SRR30337622_1.fastq.gz | Fastqsanger.gz | |||
| SRR30337622_2.fastq.gz | Fastqsanger.gz |
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Project description:Alzheimer's disease (AD) is a multifactorial disorder with serious social, health, and economic implications, affecting over 30 million individuals worldwide, and this number may triple by the year 2050. To date, there are no accurate biomarkers for early diagnosis nor effective treatments to delay the progression of the disease. AD is characterized by extracellular senile plaques, intracellular neurofibrillary tangles, microglia activation, synapse loss, and inflammation leading to neuronal degeneration and cognitive decline. However, the molecular mechanisms underlying this inflammatory process are not fully understood. In this sense, increased levels of KChIP3 in the brains of postmortem AD patients and AD mouse models have been reported. Here, we propose that KChIP3 participates in AD development by maintaining an inflammatory state that negatively impacts cognitive functions. To test this hypothesis, we knock out the expression of KChIP3 in the AD mouse model 5XFAD (5XFAD/KChIP3-/-). We discovered that the absence of KChIP3 reduces the learning and memory capacity of the 5XFAD mice, reduces hippocampal inflammatory molecules and beta-amyloid plaque deposition, and rescued the reduced number and length of hippocampal dendrites and LTP in the 5XFAD mice. Transcriptomic and quantitative proteomic approaches revealed decreased levels of inflammatory mediators and enrichment of molecules related to synaptic transmission, LTP, and learning and memory in the hippocampus of 5XFAD/KChIP3-/-. Our data point out KChIP3 as a therapeutic target to restore the central nervous system's immune suppressive status, favoring the protective effect of the innate immune response in Alzheimer´s disease.
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