Sgk1, a new target for Alzheimer's disease

Neurodegenerative diseases such as Alzheimer's disease (AD) and frontal lobe dementia (FTD) are the leading causes of dementia in older patients and still lack effective treatment.
have shown that an ontological genetic disorder can lead to changes in gene expression in cognitive regions of the brain.
therefore, restoring the pre-mesogenetic stability may be beneficial for the treatment of such diseases.
In a new study published in Science Advances on December 9, researchers at the State University of New York at Buffalo found that inhibiting certain enzymes associated with abnormal gene transcription could restore memory loss associated with Alzheimer's disease, a finding that offers hope for the development of a new treatment for Alzheimer's disease.
: Science Advances First, researchers examined changes in hismoglobin methylation markers associated with gene activation or silencing in posthumous tissue and mouse models in Alzheimer's patients.
found that the expression of histogene H3K4me3 and its catalytic enzyme SET1/MLL HMT (methyl transferase) increased significantly in the frontal cortical cortical layer (PFC).
pre-cortical cortical layer is a command center with advanced "execution" functions and is a key brain region damaged by Alzheimer's disease and frontal temporal lobe dementia.
the levels of H3K4me3 and its catalytic enzymes in the pre-cortical layer increased significantly (Source: Science Advances) In the Alzheimer's mouse model, the researchers found that the systemic dosage of set1/MLL HMT inhibitor WDR5-0103 significantly reduced levels of H3K4me3 in mice, significantly improved memory-related behavior, and reversed memory impairment in mice.
and the reduction of cognitive impairment after treatment was associated with improved function and expression of glutamate-enabled synapses in the pre-frontal cortical cortical cortical layer.
further analysis of cognitive impairments in alzheimer's mice improved by using WDR5-0103 (Source: Science Advances) Showed that many of the genes in the pre-preletephal cortically increased H3K4me3 richness after Alzheimer's mice were treated with WDR5-0103.
the highest-ranked gene is Sgk1, which encodes serum and glucosal hormone-regulating kinase 1, and Sgk1, which is also significantly elevated in the pre-cortical cortical layer in Alzheimer's patients.
In mice with Alzheimer's disease, the researchers gave mice Sgk1-specific inhibitor GSK650394 the gene with the highest increase in expression and H3K4me3 occupancy (Source: Science Advances) and observed a significant decrease in high phosphorylation tau protein levels, a recovery of glutamate synapses in the prelental cortical region, and improved memory impairment in AD mice.
Inhibition of Sgk1 uplifts reduces tau excessive phosphorylation and restores glutamate-energy synth subject expression (Source: Science Advances) Overall, these results reveal a new role of higlobin methylation in the pathophysiology of Alzheimer's disease, as well as a promising treatment strategy for Alzheimer's disease and tau protein-related neurodegenerative diseases.
: Qing C., Wei W., Jamal B. W. et al. Targeting histone K4 trimethylation for treatment of cognitive and synaptic deficits in mouse models of Alzheimer's disease. Science Advances (2020)