Breaking News
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
December 10, 2018 - DDT in Alaskan fish shown to increase risk of cancer
December 10, 2018 - Laws to curb use of cell phones have greatly reduced fatalities for motorcyclists
December 10, 2018 - Argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia
December 10, 2018 - University of Maryland doctors treat first breast cancer patients with GammaPod radiotherapy
December 10, 2018 - The heartbeat seat: Demoing new well-being technologies in a car
December 10, 2018 - Leading Cancer Researcher to Direct Herbert Irving Comprehensive Cancer Center
December 10, 2018 - Study compares pain-related diagnoses in First Nations and non-First Nations children, youth
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Smart life-collar could save lives of young children
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Episodic memory tests help in predicting brain atrophy and Alzheimer’s disease
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
December 10, 2018 - Cervical cancer risk is higher in women with positive HPV, but no cellular abnormalities
December 10, 2018 - Combo therapy not needed if low RA disease activity achieved
December 10, 2018 - Novel therapeutic targets based on biology of aging show promise for Alzheimer’s disease
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Eating disorders now a top priority with Australian Government
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
December 9, 2018 - Feds say heroin, fentanyl remain biggest drug threat to US
December 9, 2018 - Eliminating microglia can reverse some aspects of stress sensitization, study shows
December 9, 2018 - New genetic insight could help treat rare debilitating heart and lung condition
December 9, 2018 - MiRagen Therapeutics Announces Final Safety, Biodistribution and Clinical Efficacy Data From Phase 1 Cobomarsen Clinical Trial in Patients With Mycosis Fungoides
December 9, 2018 - Work with your doctor to weigh pros, cons of treatment options for hyperthyroidism
December 9, 2018 - CWRU researcher secures $14.6 million funding for genetic study into Alzheimer’s disease
December 9, 2018 - High intensity statin treatment and adherence could save more lives
December 9, 2018 - Surgery patients use only 1/4 of prescribed opioids, and prescription size matters
December 9, 2018 - AXT offers Phi Optics upgrade to QPI systems for inverted light microscopes
December 9, 2018 - New booklet could help improve conditions of young pupils with albinism
December 9, 2018 - Few Physicians Work in Practices That Use Telemedicine
December 9, 2018 - Older Adults and Oral Health
December 9, 2018 - Health utility values improve after septorhinoplasty
December 9, 2018 - New EU-funded project provides insight into how the brain develops
December 9, 2018 - Expanded use of tele-emergency services can help strengthen rural hospitals
December 9, 2018 - Infections in the Young May Be Tied to Risk for Mental Illness: Study
December 9, 2018 - Profile: Native Hawaiians and Pacific Islanders
December 9, 2018 - Snoring poses greater cardiac risk to women
December 9, 2018 - Researcher takes further steps in understanding how and why cute aggression occurs
December 9, 2018 - Researchers create new light-activated tools for controlling neurons
December 9, 2018 - Spinal cord injury disrupts the body’s internal clock, study shows
December 9, 2018 - Babies recognize nested structures similar to our grammar
December 9, 2018 - UT Austin researcher receives $2.5 million CZI grant for neurodegenerative disease research
December 9, 2018 - Sleep problems found to be prevalent and increasing among college students
December 9, 2018 - Study reveals why some children are susceptible to the effects of maltreatment
Novel therapeutic approach alleviates ALS-related muscular atrophy in mouse models

Novel therapeutic approach alleviates ALS-related muscular atrophy in mouse models

image_pdfDownload PDFimage_print

Supplementing a single protein found in the spinal cord could help prevent symptoms of Lou Gehrig’s disease, according to a new study out of Case Western Reserve University School of Medicine. Researchers found high levels of the protein–called mitofusion 2 or Mfn2–prevented nerve degeneration, muscle atrophy, and paralysis in a mouse model of the disease. Since Mfn2 is often depleted during Lou Gehrig’s, the new study suggests supplementing it could be a novel therapeutic approach for the disease.

Lou Gehrig’s disease, or amyloid lateral sclerosis (ALS), is a progressive disorder that devastates motor nerve cells. People with ALS slowly lose the ability to control muscle movement, and are ultimately unable to speak, eat, move, or breathe. The cellular mechanisms behind ALS are also found in certain types of dementia. For the estimated 15,000 Americans living with ALS, the findings offer new hope for ways to delay symptoms.

“We found a way to alleviate age and ALS-related muscular atrophy in our mouse models,” said Xinglong Wang, PhD, associate professor of pathology at Case Western Reserve University School of Medicine. “Amazingly, we could delay ALS symptom onset by 67 days.”

Wang led the study, published today in Cell Metabolism, in which researchers successfully staved off muscle atrophy and paralysis simply by increasing Mfn2 levels in mouse spinal cords.

Wang and colleagues tested the most widely used ALS mouse model. They genetically engineered the diseased mice to have increased Mfn2 levels–but only in nerve cells that extend from the spinal cord and connect to muscle fibers. In late stages of the disease, mice with high Mfn2 levels in these nerves were a healthy weight, and did not have any of the muscle atrophy, gait abnormalities, or reduced grip strength that mice in control groups developed. Even mice who underwent heavy sciatic nerve damage benefited from elevated Mfn2 levels.

Said Wang, “Upregulation of Mfn2 specifically in nerve cells is sufficient to abolish skeletal muscle loss in ALS and aged mice, despite ALS-causing protein being found in all organs and tissues.”

By studying nerve cells collected from the mice, Wang’s team uncovered how Mfn2 offers its protective effects. The researchers found Mfn2 coexists with nutrients in cell structures called mitochondria. Their experiments showed mitochondria travel along nerve cell extensions–axons–and deliver the nutrients to the point where nerve cells and muscle fibers meet. This preserves sensitive connections–synapses–between nerve and muscle cells and prevents muscle atrophy. “We found mitochondria function as miniature ‘trucks’ to transport protein along axons to prevent synaptic degeneration,” explained Wang.

Cellular transport is not typically in the job description for mitochondria. The ancient cellular structures are well-known to be “powerhouses of the cell”–producing energy that keeps cells running. According to Wang, “this is a novel, previously unrecognized role for mitochondria.”

Specifically, Wang’s team found mitochondria use Mfn2 on their surfaces to carry a nutrient called calpstatin. Calpstatin inhibits harmful enzymes that break down nerves and muscle fibers. With the help of Mfn2, mitochondria carry calpstatin along nerve cells axons to meet muscle cells. There, calpstatin prevents enzymes from destroying delicate synapse connections. But without Mfn2, mitochondria can’t carry the nutrient.

According to Wang, the findings have broad implications. “Mfn2 deficiency or mutations are commonly observed in patients with ALS, peripheral neuropathy, Alzheimer’s disease, and other neurodegenerative diseases in which synaptic loss has long been recognized as a prominent early feature,” he says. “Supplementing Mfn2 may be a common and effective therapeutic approach to treat a wide range of diseases including but not limited muscular disorders, patients with nerve injury and various major neurodegenerative diseases associated with synaptic loss.”

Source:

http://casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=1350&news_category=8

Tagged with:

About author

Related Articles