Acidification of the intracellular environment can remove amyloid

Recently, researchers from the University of Texas published a research paper in the journal eLife

Studies have shown that when genetic technology is used to turn off the NHE6 gene, the pH of brain cells will be acidified, thereby eliminating the formation of amyloid plaques in Alzheimer's disease mouse models and preventing the accumulation of amyloid

Early studies have shown that the most important genetic risk factor for late-onset Alzheimer's disease is apolipoprotein (ApoE4), which is one of three variants of a protein involved in fat metabolism in mammals

In humans, the average age of onset of Alzheimer's disease with ApoE4 variants has been reduced by several years compared with the most common ApoE3 variant, and the more rare ApoE2 seems to have a protective effect on this disease

The three variants are very similar in structure

In this study, the researchers focused on the organelles responsible for protein sorting, recycling, or transporting proteins to the lysosome through the interior of the cell

The researchers used genetically modified mice to mimic Alzheimer's disease and produce human forms of ApoE4 and amyloid

However, this aggregation prevents these organelles from continuing to transport, recirculate, or help process other proteins, including amyloid

When the researchers used genetic technology to turn off a gene called NHE6, they found that the negative effects of ApoE4 were eliminated, and there was no obstacle to the transport of this protein within the cell

When the researchers turned off the NHE6 gene, it no longer produced pH-regulating proteins, and the organelles quickly became more acidic.

Turning off the NHE6 gene prevents the accumulation of beta amyloid

It is worth noting that inhibiting the NHE6 gene in mice can effectively inhibit the deposition of amyloid even in the absence of ApoE4, which indicates that the accelerated acidification of organelles caused by the lack of NHE6 can prevent the formation of amyloid plaques

Therefore, inhibiting or inhibiting NHE6 may be a universal, ApoE-independent method to prevent the accumulation of amyloid in the brain

In conclusion, studies have shown that organelle acidification has considerable potential.