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Ube2h gene

What Are Alzheimer’s Biomarkers, and Why Should We Care About Ube2h?

By | May 22nd, 2020

A research team at the Korea Brain Research Institute discovered, for the first time, an increased specific expression of the Ube2h gene in the blood of people living with Alzheimer’s, publishing their findings in International Journal of Molecular Sciences (IJMS).

The study links certain enzymes with degenerative brain diseases, which could mean scientists and drugmakers now have a new biomarker for the diagnosis of Alzheimer’s and dementia.

What’s a Biomarker, and Why Does It Matter?

Biomarkers — from a portmanteau of “biological marker” — are a broad subcategory of medical indicators of risk of a disease, which doctors or scientists are able to measure accurately and reproducibly.

According to doctors Kyle Strimbu and Jorge A. Tavel, biomarkers are “by definition objective, quantifiable characteristics of biological processes.” They might, but don’t necessarily, correlate with a person’s experience and sense of wellbeing, and in fact, they are often present without any visible effect on a person’s health or symptoms. Examples of biomarkers might include pulse or blood pressure, all the way down to the presence of a certain gene.

When it comes to Alzheimer’s, biomarkers that scientists have linked to the development of Alzheimer’s or other dementias, there are a number of genes, such as APOE, that scientists suspect have a causal relationship to the beta-amyloid plaque and tau tangles which lead to dementia.

These are among the biomarkers used as reference in the research of Alzheimer’s disease. And although no cure has been found, scientists around the world are making headway in the last few months on finding new paths to a cure by focusing their attention on the search for other biomarkers.

One possibility is a gene called PHGDH, which produces a nucleic acid located in all cells called RNA. A recent study found that about two years before a participants were diagnosed with Alzheimer’s, they showed heightened levels of RNA production on account of increased PHGDH activity.

Earlier this year, mutations of a gene called PSEN1 have also been linked to early onset Alzheimer’s, as has the gene Aggregatin, as well as certain cellular formations in the brain. In April 2020, the largest Alzheimer’s and proteins study to date found that the glucose metabolism of the brain’s support cells may serve as a biomarker in spinal fluid tests, meaning researchers had yet another possible drug target to develop an Alzheimer’s cure.

The search for new biomarkers is fueled by the knowledge that a cure cannot come soon enough, and each new Alzheimer’s biomarker definitively identified could be the key to unlocking it.

What is Ube2h?

To maintain homeostasis, our body continually creates and breaks down protein. Once the proteins in a cell reach the end of their lifespan, a small protein called ubiquitin attaches to them and, in a process called ubiquitination, they are broken down. If something goes awry during this protein degradation process, extra proteins accumulate inside our cells, leading to cancer and other diseases.

The Korean research team discovered that one of the enzymes critical to this degradation of protein cells, an enzyme called E2, is over-expressed in both people and mice with Alzheimer’s. That led them to the consistent increased expression of Ube2h.

Scientists studied the impact on known biomarkers, such as the tau protein, when Ube2h was suppressed, and their findings suggest that Ube2h is able to regulate the expression of Alzheimer’s-related proteins. Now, the researchers say, Ube2h should be studied further as a possible new diagnostic indicator, and thereby, a possible new route to an Alzheimer’s cure.

What’s Next?

“We are working to discover Alzheimer’s Disease-specific genes using next-generation sequencing (NGS) and to make use of such findings by establishing a big data set,” said Dr. Jae-Yeol Joo, a senior researcher at KBRI. “For the research community, we will provide a platform for follow-up research. For industry, we hope our technology can be applied to ensure the quick and precise diagnosis and treatment of dementia.”

A patent has been filed for an Alzheimer’s diagnosis and treatment method that would center on the detection of the Ube2h gene. Next steps for the team include transferring this technology to companies to help facilitate the development of diagnosis kits that utilize this possible new approach.

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