Toxic Protein Could Be Behind the Development of Amyotrophic Lateral Sclerosis
New research has found that a toxic protein may affect the skeletal muscle tissues, spinal cord, and brain, aiding the development and progression of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis or ALS in short, is an illness that affects an individual’s nervous system, causing nerve cells in the spinal cord and brain to degenerate. As it progresses, this motor neuron illness leads to muscle weakness and atrophy.
The research was carried out by a team of scientists from Penn State College of Medicine. It was based on prior studies which implicated mutations of the superoxide dismutase 1 (SOD1) protein in roughly 20% of ALS cases. The researchers explained that SOD1, which normally comprised of 2 identical units (dimer), gained a toxic function when it structured itself into a form with 3 units (trimer).
Prof. Nikolay Dokholyan, the senior author of the study, explained that SOD1 trimers were associated with increased cell death in ALS models.
The objective of this latest study was to learn more about the role the protein’s mutations played in cell degeneration and dysfunction. For their research, the scientists introduced SOD1 dimers and trimers into the spinal cord, brain, and muscle tissues of mice which were divided into 2 groups.
They then looked out for proteins that bound to the trimers and compared them to those that bound themselves to the dimers.
The study’s co-author, Brianna Hnath, explained that their focus was finding new proteins that’d interact with this toxic protein. The scientists discovered that the trimers interacted with different proteins, depending on the tissue type. This, they theorized, could partly explain the multifaceted nature of ALS.
In muscle tissues, the trimers bound themselves to proteins involved in metabolic processes, which could hamper metabolism and energy production in muscle cells. In spinal cord and brain tissue, the trimers bound themselves to proteins that played a role in maintaining neuron function, structure, and communication between nerve cells.
The scientists found that the trimers also activated pathways linked to cellular aging, which could contribute to neuronal degeneration and dysfunction. In addition, they determined that trimers bound themselves to the septin-7 protein, which plays a role in vital nerve cell processes like maintaining communication and cellular structure.
They explained that septin-7 binding to SOD1 could disrupt these functions, giving rise to neuron degeneration.
This research brings scientists one step closer to better understanding the physiological processes that cause ALS and may aid in the identification of therapeutic targets for future treatments. Their findings were reported in the Structure journal.
As more becomes known about the specific mechanisms through which diseases like ALS develop, drug makers like Clene Inc. (NASDAQ: CLNN) have an improved chance of bringing to market effective treatments that will address the clinical needs of patients.
NOTE TO INVESTORS: The latest news and updates relating to Clene Inc. (NASDAQ: CLNN) are available in the company’s newsroom at https://ibn.fm/CLNN
Please see full terms of use and disclaimers on the BioMedWire website applicable to all content provided by BMW, wherever published or re-published: http://BMW.fm/Disclaimer
New research has found that a toxic protein may affect the skeletal muscle tissues, spinal cord, and brain, aiding the development and progression of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis or ALS in short, is an illness that affects an individual’s nervous system, causing nerve cells in the spinal cord and brain to degenerate. As it progresses, this motor neuron illness leads to muscle weakness and atrophy.
The research was carried out by a team of scientists from Penn State College of Medicine. It was based on prior studies which implicated mutations of the superoxide dismutase 1 (SOD1) protein in roughly 20% of ALS cases. The researchers explained that SOD1, which normally comprised of 2 identical units (dimer), gained a toxic function when it structured itself into a form with 3 units (trimer).
Prof. Nikolay Dokholyan, the senior author of the study, explained that SOD1 trimers were associated with increased cell death in ALS models.
The objective of this latest study was to learn more about the role the protein’s mutations played in cell degeneration and dysfunction. For their research, the scientists introduced SOD1 dimers and trimers into the spinal cord, brain, and muscle tissues of mice which were divided into 2 groups.
They then looked out for proteins that bound to the trimers and compared them to those that bound themselves to the dimers.
The study’s co-author, Brianna Hnath, explained that their focus was finding new proteins that’d interact with this toxic protein. The scientists discovered that the trimers interacted with different proteins, depending on the tissue type. This, they theorized, could partly explain the multifaceted nature of ALS.
In muscle tissues, the trimers bound themselves to proteins involved in metabolic processes, which could hamper metabolism and energy production in muscle cells. In spinal cord and brain tissue, the trimers bound themselves to proteins that played a role in maintaining neuron function, structure, and communication between nerve cells.
The scientists found that the trimers also activated pathways linked to cellular aging, which could contribute to neuronal degeneration and dysfunction. In addition, they determined that trimers bound themselves to the septin-7 protein, which plays a role in vital nerve cell processes like maintaining communication and cellular structure.
They explained that septin-7 binding to SOD1 could disrupt these functions, giving rise to neuron degeneration.
This research brings scientists one step closer to better understanding the physiological processes that cause ALS and may aid in the identification of therapeutic targets for future treatments. Their findings were reported in the Structure journal.
As more becomes known about the specific mechanisms through which diseases like ALS develop, drug makers like Clene Inc. (NASDAQ: CLNN) have an improved chance of bringing to market effective treatments that will address the clinical needs of patients.
NOTE TO INVESTORS: The latest news and updates relating to Clene Inc. (NASDAQ: CLNN) are available in the company’s newsroom at https://ibn.fm/CLNN
Please see full terms of use and disclaimers on the BioMedWire website applicable to all content provided by BMW, wherever published or re-published: http://BMW.fm/Disclaimer
