A new target for Alzheimer's disease - MEF2

SourceMedicine Cube Pro

Author: Li Yuan

As we age and age, many people develop dementias, such as Alzheimer's

However, a small number of individuals with pathological features of neurodegenerative diseases are able to maintain normal cognition, an ability known as cognitive resilience (CgR)

In a new study published Nov.

Source: Science Translational Medicine

First, the researchers analyzed molecular changes in mice with different environmental richness.

Environmental richness-induced transcriptional signatures associated with MEF2 activity (Source: Science Translational Medicine)

And when the researchers knocked down the MEF2 gene in the frontal cortex of wild-type mice, the mice developed cognitive impairment, no longer able to reap the cognitive benefits of the enriched environment, and neurons became hyperexcited

Deletion of the MEF2 gene in the mouse frontal cortex impairs cognition in mice and causes neuronal hyperexcitability (Source: Science Translational Medicine)

After analyzing human data from both datasets, the researchers found that cognitive resilience is highly correlated with MEF2 and the expression of many genes that MEF2 regulates, including those encoding ion channels, which control neuronal excitability

The MEF2 transcriptional network has been implicated in human cognition and cognitive resilience (Source: Science Translational Medicine)

The researchers then explored whether MEF2 could reverse cognitive impairment in a mouse model of tauopathy

MEF2 overexpression improves cognition and rescues tauopathy-induced hyperexcitability in a mouse model of neurodegeneration (Source: Science Translational Medicine)

Overall, this study sheds light on the role of MEF2 in promoting cognitive resilience, highlighting the potential of MEF2 as a biomarker or therapeutic target for neurodegeneration and healthy aging

References:

[1] Barker SJ, Raju RM, Milman NEP, et al.

[2] Study links gene to cognitive resilience in the elderly (Source: MIT News)