As the year draws to a close, the Office of Communications is rerunning some of the biggest and most read articles posted in 2022.Its topics include his UMass Chan study that guided the FDA on his rapid COVID-19 testing recommendations, the regional medical campus with Burlington’s Lahey Hospital and Medical Center and boston globe‘s Top Places to Work list included UMass Chan for the first time.Look for these stories UMass Chan News From December 21st to December 30th. This article was originally published by him on March 10th.
An international research team has found that inorganic polyphosphate released by nerve cells known as astrocytes in people with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is responsible for these diseases. found to contribute to the characteristic motor neuron death. The study is by Dr. Brigitte van Zundert, adjunct professor of neurology at UMass Chan and professor at Andres Her Vero University in Chile. Robert H. Brown Jr., DPhil, MD, Professor of Neurology, and His Colleagues Appear This Week neuron.
“We are encouraged by these early results,” said Dr. Brown. Leo P. and Theresa M. LaChance Medical Research Chair“These findings provide an entirely new perspective on ALS pathogenesis and offer exciting hypotheses and possibilities for both disease biomarkers and therapeutic targets.”
ALS and FTD are characterized by degeneration of motor neurons in the spinal cord and frontal lobe, but the cause of this neurotoxicity remains elusive. And while great progress has been made in identifying the genetic mutations responsible for these neurodegenerative diseases, the vast majority of cases lack an identifiable genetic mutation. and the possible effects of virulence factors also remain elusive.
Previous studies have shown that astrocytes (glial cells in the brain and spinal cord) can release one or more virulence factors that contribute to motor neuron death.of neuron Studies provide evidence that the neurotoxic agent in question is a common inorganic polyphosphate. It has been found to be released by both mouse and human astrocytes in cells with a range of ALS/FTD-associated mutations (including SOD1, TARDBP, and C9ORF72).
A virulence factor called polyP is a ubiquitous negatively charged inorganic biopolymer present in the cells of all organisms, from bacteria to mammals. These polyphosphates serve numerous functions in the cell, including energy storage, membrane channel formation, gene activity regulation, enzyme regulation, and stress response.
“The biggest surprise of our study is that the virulence factor is not a novel or rare protein or peptide, but is found in all tested cell types in nature and is highly conserved over more than 3 billion years of evolution.” It is a simple, inorganic molecule,” said Dr. van Zundert, corresponding author of . neuron study.
A key finding of this study is that human cerebrospinal fluid samples from familial and sporadic ALS cases revealed increased polyp concentrations.
“This study shows that exposure of spinal cord neurons to polyP recapitulates the toxic effects of medium from ALS astrocyte cultures, causing hyperexcitability, increasing Ca2+ influx into neurons, and promoting motor neuron death. It shows that it will be done,” van Zundert said.
Furthermore, van Zundert, Brown and colleagues found that reducing polyp levels can rescue motor neurons from astrocyte toxicity.
“Our findings strongly support the view that reducing extracellular polyp levels may be an innovative therapeutic strategy for different types of ALS/FTD,” said van Zundert. says.
As a postdoctoral fellow in Brown’s lab in 2008, van Zundert discovered that increased electrical excitability of motor neurons was an early key feature in a mouse model of ALS. van Zundert began considering polyps as a possible cause of hyperexcitability in 2014. It was reported that this molecule may function as a glial transmitter mediating communication between astrocytes and neurons.
ALS and FTD are devastating, incurable diseases. ALS is a progressive neurodegenerative disease with loss of motor neurons that control voluntary muscles. About 10% of ALS are familial, inherited from both parents and caused by genetic mutations in the patient’s DNA. The remaining 90% of cases are classified as sporadic and occur in cases with no family history. An estimated 6,000 people are diagnosed with ALS each year in the United States.
Similarly, FTD, originally called Pick’s disease, is one of the most common early-onset dementias after Alzheimer’s disease. FTD is caused by loss of neurons in the frontal or temporal lobes.
This research was supported by several funding agencies, including the ALS Association, Angel Fund for ALS Research, ALS Therapy Alliance, ALS Finding a Cure, ALS ONE, Max Rosenfeld ALS Research Fund, FightMND, with additional contributions from national laboratories. I got help. Health and some Chilean government agencies.
Related UMass Chan news articles:
UMass Chan ALS paper selected for STAT Madness
UMass Chan Founds Translational Institute for Molecular Therapeutics
UMass Alumni Dan and Diane Riccio Pledge $15 Million to Advance ALS, Neuroscience Research
UMass Chan’s Clinical Trial Shows Antisense Oligonucleotides Safely Suppress Mutant ALS Gene in Pilot Human Study