Igf2Bp2-Mediated M6A Modification Of Igf1R Mrna Promotes Neuronal Senescence And Cognitive Decline In Alzheimer’S Disease
Alzheimer’s disease, a devastating condition leading to memory loss and cognitive decline, is increasingly linked to the premature aging of brain cells, a process known as neuronal senescence. Recent research has shed light on a crucial player in this process: a protein called IGF2BP2. This protein was found to be significantly elevated in the brain cells of models mimicking Alzheimer’s disease.
So, what does IGF2BP2 do? It acts on another molecule called IGF1R mRNA. mRNA is like a blueprint that carries instructions from our DNA to make proteins. IGF2BP2 stabilizes this IGF1R mRNA through a specific chemical tag known as m6A modification. Think of m6A modification as a sticky note on the blueprint that tells the cell to keep it around longer.
When IGF1R mRNA is stabilized, it leads to more IGF1R protein being produced. This increase in IGF1R then accelerates the aging of brain cells, contributing to the damage seen in Alzheimer’s.
However, the good news is that when researchers reduced the levels of IGF2BP2, they observed remarkable improvements. In Alzheimer’s models, lowering IGF2BP2 not only improved cognitive function but also reduced the accumulation of harmful amyloid-beta (Aβ) plaques—a hallmark of the disease—and delayed the aging of brain cells.
These findings suggest that targeting IGF2BP2 and its role in m6A modification could open new avenues for developing treatments to combat neuronal senescence and cognitive decline in Alzheimer’s disease.
Source: link to paper