December 8, 2022

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Protein linked to significantly increased risk of Alzheimer’s disease



 

New Study: Protein linked to significantly increased risk of Alzheimer’s disease.

Mutations in a newly identified small protein are associated with a substantially increased risk of Alzheimer’s disease , according to a new study from the University of Southern California (USC) Leonard Davis School of Aging .

This expands the known genetic targets for the disease and suggests a new potential therapeutic avenue.

 

Protein linked to significantly increased risk of Alzheimer's disease

 

 

The protein, called SHMOOSE, is a tiny “microprotein” encoded by a newly discovered gene in the energy-producing mitochondria within cells.

Mutations in this gene partially inactivate the SHMOOSE microprotein and were associated with a 30% increased risk of Alzheimer’s disease in four different cohorts.

According to the researchers, almost 25 percent of people of European ancestry have a mutated version of the protein.

 

Alzheimer’s disease is the most common type of dementia.

It is a progressive disorder that begins with mild memory loss that can lead to a loss of the ability to hold conversations and respond to the environment.

In 2020, as many as 5.8 million Americans will have Alzheimer’s disease, according to the Centers for Disease Control and Prevention (CDC).

 

The study was published Sept. 21 in the journal Molecular Psychiatry .

 

The enormous risk and high prevalence of this previously undiscovered mutation distinguishes it from other proteins implicated in Alzheimer’s disease, the researchers said. Except for APOE4 — the most powerful known genetic risk factor for the disease — only a limited number of other gene mutations have been identified, and these mutations only marginally increase risk by less than 10 percent.

Furthermore, since the microprotein is about the same size as the insulin peptide, it can be easily administered. This greatly increases its therapeutic potential.

 

Protein linked to significantly increased risk of Alzheimer's disease

 

 

 

“This discovery opens up exciting new directions for developing precision medicine-based treatments for Alzheimer’s disease, with a focus on SHMOOSE as a target area,” said Pinchas Cohen, senior author of the study and senior author of the study. Professor of Medicine, Medicine and Biological Sciences. “Administration of SHMOOSE analogs to individuals who carry the mutation and produce the mutant protein may prove beneficial in neurodegenerative and other diseases of aging.”

 

USC neuroscience PhD graduate Brendan Miller is the study’s lead author. He uses big data techniques to identify genetic variants in mitochondrial DNA that are associated with disease risk.

After analyzing a gene mutation that increased Alzheimer’s disease risk, brain shrinkage and energy metabolism, Miller and his colleagues discovered that the mutated gene encodes the SHMOOSE microprotein and set out to study its mutant and default forms.

SHMOOSE is the first mitochondrial DNA-encoded microprotein to be detected using antibodies and mass spectrometry, the researchers said.

 

It appears that this microprotein modifies energy signaling and metabolism in the central nervous system.

It is found in the mitochondria of neurons, and its levels in the cerebrospinal fluid correlate with biomarkers of Alzheimer’s disease.

Various cell culture and animal experiments have shown that SHMOOSE partially alters energy metabolism in the brain by inhabiting a key part of the mitochondria, the inner mitochondrial membrane.

 

Alzheimer’s disease is currently ranked as the sixth leading cause of death in the United States.

However, recent estimates from the CDC suggest the disease may rank third, after heart disease and cancer, as a cause of death in older adults.

Although there is currently no cure for Alzheimer’s disease, significant progress has been made in developing and testing new treatments in recent years.

 

 

 

 

An emerging field of research

According to Miller, the findings highlight the importance of the relatively new field of microproteins.

For decades, scientists have studied biology primarily by considering a set of 20,000 large protein-coding genes.

However, there are hundreds of thousands more possible genes encoding tiny microproteins that have been revealed by modern technology.

 

“The field of microproteins is still so new,” Miller said. “We don’t yet know how many microprotein genes are even functional, and it would be prohibitively expensive and expensive to go through a list of thousands of potential microproteins one by one.” Inefficient.

The method my colleagues and I used to detect SHMOOSE shows the power of combining large genetic data with molecular and biochemical techniques to discover functional microproteins.”

 

 

 

 

Protein linked to significantly increased risk of Alzheimer’s disease

(source:internet, reference only)


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