Researchers discover a receptor and protein associated with Lou Gehrig's disease

NewsGuard 100/100 Score

Researchers at Nagoya University in Japan have discovered a receptor, sigma-1 receptor, and a protein, ATAD3A, that are associated with Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease. Since there are drugs that specifically target the receptor, their findings suggest a new therapeutic strategy. They published the study in the journal Neurobiology of Disease.

ALS causes degeneration of motor neurons and the resulting muscle atrophy. Some of this degeneration is the result of the dysfunction of mitochondria, the energy-generating organelles of the body. This dysfunction causes a lack of energy in neurons resulting in the characteristic symptoms of the disease.

The integrity of the mitochondria-associated membrane (MAM) is important for the stability of the mitochondria. The MAM is especially important during the processes of division of mitochondria (called fission) and mitochondria fusing together (called fusion). Several proteins, including enzymes, are associated with these processes and accumulate in the MAM.

In patients with ALS, the mitochondria are damaged and undergo a process called fragmentation, which is associated with decreased cell fusion and increased fission. As cells increasingly divide, mitochondria break down into smaller organelles that have impaired function.

"Researchers have found this process of fragmentation in various neurodegenerative diseases," said Professor Koji Yamanaka (he/him). "Discovering the detailed mechanism of how this process occurs would be useful to treat not only ALS but also other diseases."

Since proteins rarely show activity on their own, to exert an effect, they often form assemblies, called dimers. A protein found in the MAM, called ATAD3A, is often found in dimers that cause mitochondrial dysfunction. Because these dimers have been found in diseases that cause nerve cells to die, such as Huntington's and Alzheimer's, Yamanaka and his colleagues tested whether ATAD3A could also be involved in patients with ALS.

The group consisted of Professor Koji Yamanaka, Assistant Professor Seiji Watanabe (he/him), and graduate student Mai Horiuchi (she/her) at the Research Institute of Environmental Medicine at Nagoya University. They found that the interaction between ATAD3A and a receptor, called the sigma-1 receptor, contributes to the homeostasis of the MAM. When they tested models deficient in sigma-1 receptor-ATAD3A, they found they were associated with mitochondrial fragmentation.

Loss of sigma-1 receptor function causes the inherited form of ALS. In healthy subjects, the sigma-1 receptor interacts with ATAD3A to suppress mitochondrial fragmentation. Both the sigma-1 receptor and ATAD3A are critical factors of MAM to maintain mitochondrial homeostasis, and we found that they are altered in the mouse model of ALS."

Professor Koji Yamanaka, Nagoya University

Their findings also suggest potential treatments for patients with ALS. "Administration of a sigma 1 receptor agonist extended the survival time of ALS model mice," Yamanaka explains. "Targeting sigma-1 receptor-ATAD3A at the MAM to prevent mitochondrial dysfunction would lead to the development of a novel therapeutic strategy for neurodegenerative diseases and may be a suitable target for future drug development for ALS."

Journal reference:

Watanabe, S., et al. (2023). Sigma-1 receptor maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation at the mitochondria-associated membrane in amyotrophic lateral sclerosis. Neurobiology of Disease.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Protein intake during pregnancy affects offspring's facial features