Breaking News
April 20, 2018 - FDA Alert: NxtGen Botanicals Maeng Da Kratom by NGB Corp.: Recall
April 20, 2018 - Pelizaeus-Merzbacher-like disease type 1 – Genetics Home Reference
April 20, 2018 - Tick-borne diseases reach epidemic levels, panel says
April 20, 2018 - A potential “male pill” without side effects
April 20, 2018 - Researchers discover new information related to rare form of leukemia
April 20, 2018 - Researchers find crucial links between dopamine and avoidance behavior
April 20, 2018 - UGA scientist creates system for efficient detection of foodborne pathogens
April 20, 2018 - Social Support of Autonomy Tied to Better Glycemic Control in DM
April 20, 2018 - Study reports use of nutritional ketosis with mobile app intervention could reverse Type 2 diabetes
April 20, 2018 - New microscopy techniques allow quasi-biochemical studies on living T cells
April 20, 2018 - Study shows connection between muscular strength and brain health
April 20, 2018 - Ecolab introduces Life Sciences cleanroom program in North America
April 20, 2018 - Male fruit flies like sex and alcohol
April 20, 2018 - Improving job prospects unlikely to control opioid epidemic
April 20, 2018 - Skin Sensor Might Someday Track Alcoholics’ Booze Intake
April 20, 2018 - The relevance of GABA for diabetes highlighted in two new studies
April 20, 2018 - Novel method enables fast and noninvasive assessment of tumor status
April 20, 2018 - IU psychologist receives NIH grant to study earliest phases of language learning in children
April 20, 2018 - Walking fast lowers risk of hospitalization in heart patients, shows study
April 20, 2018 - Young victims of cyberbullying twice as likely to attempt suicide and enact suicidal behavior
April 20, 2018 - Role of UBE3A enzyme in Angelman syndrome
April 20, 2018 - NovaDigm Therapeutics initiates NDV-3A Phase 2a study for reduction of S. aureus in military trainees
April 20, 2018 - High-tech microscope reveals how cancer-causing virus anchors itself to human DNA
April 20, 2018 - Experimental compound reduces destructive inflammation to improve stroke outcome
April 20, 2018 - The May issue of Drug Discovery Today is a Special Issue and will be published very soon
April 20, 2018 - Larger families linked to heightened tooth loss risk for moms
April 20, 2018 - Scientists develop tiny fluorescent probe that seeks out GLUT5 and detects cancer cells
April 20, 2018 - The Swedish Childhood Cancer Foundation awards grant to KI researchers
April 20, 2018 - AMSBIO’s MC-Easy minicircle technology allows sustained transgene expression in quiescent cells and tissues
April 20, 2018 - Researchers use optogenetics to treat chronic pain
April 20, 2018 - Discovery of 100 new genes may aid research into pigmentation
April 20, 2018 - AYOXXA introduces new LUNARIS Mouse 12-Plex Th17 Kit for quantitative analysis of Th17 cell biology
April 20, 2018 - Compound derived from immune cells treats psoriasis in mice
April 20, 2018 - GABA-transaminase deficiency – Genetics Home Reference
April 20, 2018 - Key heart risks decline for older Americans
April 20, 2018 - UD professor wins $2.3 million grant from NIH for research on Achilles tendinopathy
April 20, 2018 - Researchers discover unique protein in malaria parasite that could be new drug target
April 20, 2018 - Bio-Techne expands automation capabilities of popular RNAscope ISH technology
April 20, 2018 - Smartphone app effective in promoting proper child car seat practices
April 20, 2018 - Nutraceuticals could play an important role in preventing heart disease
April 20, 2018 - FDA Alert: Certain Kratom-Containing Powder Products by Viable Solutions: Recall -Possible Salmonella Contamination
April 20, 2018 - What is heart failure?
April 20, 2018 - TIP Biosystems introduces handheld UV-Visible spectrophotometer for photometric measurements
April 20, 2018 - Inactivity of astronauts during spaceflights may have more pronounced effect on skeletal muscle than hypoxia
April 20, 2018 - New SIDS Info app seeks to reduce infant sleep-related deaths
April 20, 2018 - Wide-scale distribution of naloxone effectively prevents overdose deaths, study finds
April 20, 2018 - Triple-negative breast cancer found to be chemoresistant prior to treatment
April 20, 2018 - ACL tears occur the same way in women and men, study finds
April 20, 2018 - UT Southwestern researchers identify 170 potential therapeutic targets for lung cancer
April 20, 2018 - Finding the ‘keyhole’ to beat obesity at the cellular level
April 20, 2018 - Long-term exposure to cold temperatures reduces diabetes and obesity, shows study
April 20, 2018 - Metabolic Syndrome Common With Chronic Hep B Infection
April 20, 2018 - Tracking quality of life during prostate cancer treatment
April 20, 2018 - Study shows presence of beta-amyloid dimers in the brains of Alzheimer’s patients
April 20, 2018 - Researchers identify link between physical inactivity and increased risk of dying from cancer
April 20, 2018 - Breathtaking evolution amongst Indonesian tribe
April 20, 2018 - Study shows testosterone deficiency in men is associated with chronic diseases
April 20, 2018 - Simple one-page form helps improve satisfaction of patients with care
April 20, 2018 - Researchers evaluate accuracy of simple blood test to predict lung cancer
April 20, 2018 - Study looks at sperm producing ability in testicular cancer patients
April 20, 2018 - Exercise In, Vitamin D Out for Preventing Falls: U.S. Panel
April 20, 2018 - Skin cancers associated with decreased risk of developing AD
April 20, 2018 - Preserving fertility during chemotherapy
April 20, 2018 - Teva and Procter & Gamble Company terminate PGT Healthcare partnership
April 20, 2018 - People diagnosed with traumatic brain injury may have increased risk of Parkinson’s disease, shows study
April 20, 2018 - Researchers use smartphone to diagnose people infected with Loa loa worm
April 20, 2018 - College students with autism have high rate of suicidal thoughts
April 20, 2018 - Study sheds light on how the HSC niche is maintained
April 20, 2018 - Drug test spurs frank talk between hypertension patients and doctors
April 19, 2018 - Low-cost deworming drug improves female farmers’ physical fitness
April 19, 2018 - Genome editing identifies neural circuit behind leptin’s anti-obesity and anti-diabetes effects
April 19, 2018 - Many European countries lack comprehensive policy to eliminate viral hepatitis
April 19, 2018 - Young people with ADHD ‘more likely’ to come from deprived neighbourhoods
April 19, 2018 - SLU professor discovers new biomarkers for chlorine gas exposure
April 19, 2018 - Study proposes new mechanism that may contribute to gender differences in weight control
April 19, 2018 - Sleep restriction therapy does not interfere with insomnia patient’s driving ability, research shows
April 19, 2018 - Deep brain stimulation offers relief to UTHealth patient with treatment-resistant depression
April 19, 2018 - Study shows fatty fish and camelina oil boost HDL and IDL cholesterol
April 19, 2018 - FDA Alert: Euphoric Capsules by Epic Products: Recall
April 19, 2018 - Researchers identify peptide produced during cartilage deterioration as a potential source of osteoarthritis pain
USC scientists uncover cellular mechanism responsible for ALS and frontotemporal dementia

USC scientists uncover cellular mechanism responsible for ALS and frontotemporal dementia

image_pdfDownload PDFimage_print

Scientists have for the first time discovered a mechanism that limits the number of “cellular janitors” in the nervous system, leading to increased risk for two neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, according to a Keck School of Medicine of USC study published today in Nature Medicine.

In the study, Yingxiao “TK” Shi and Shaoyu Sebastian Lin in the Justin Ichida Laboratory at USC Stem Cell describe how a mutation in a gene called C9ORF72 leads to toxicity in nerve cells. It causes 10 percent of all cases of ALS and an additional 10 percent of frontotemporal dementia.

“We figured out how the most common form of ALS causes nerve cell death, and nerve cell death is what causes patients to become paralyzed or lose control of neuromuscular functions,” said Ichida, an assistant professor of stem cell and regenerative medicine at the Keck School of Medicine and a New York Stem Cell Foundation-Robertson Investigator.

Damage begins as a cellular chain reaction. Normally, the C9ORF72 gene, or C9, produces a protein that is required to make lysosomes, which act as cellular janitors to capture and remove toxic proteins and garbage. Without a normal amount of lysosomes, motor nerve cells accumulate toxic garbage and die.

To understand how this happens, the researchers extracted blood from ALS patients carrying the C9 mutation and reprogrammed these blood cells into motor nerve cells that degenerate and die in the disease. They also extracted blood from healthy patients, reprogrammed these blood cells into motor nerve cells and used gene editing to delete the C9 gene.

Whether patient-derived or gene-edited, all motor nerve cells with the mutation had reduced amounts of the protein normally made by the C9 gene. And by adding the supplemental C9 protein, the researchers could stop the motor nerve cells from degenerating.

“The C9 protein is required to construct the janitors of the cells, which are the lysosomes, and without them you have buildup of proteins in the cell that become a kind of toxic agent that causes the cells to die,” Ichida said.

Specifically, insufficient lysosomes cause cells to accumulate two key types of garbage: a big, toxic protein produced by the mutated C9 gene and molecules that receive signals from a neurotransmitter known as glutamate. Too much glutamate hyperstimulates motor nerve cells to death, a phenomenon known as “excitotoxicity.”

Guided by these discoveries, the Ichida Lab is now using the patient-derived motor nerve cells to test thousands of potential drugs, with focus on those that affect lysosomes. The goal is to find potential drugs that slow or stop degeneration of these motor nerve cells in petri dishes – and eventually in patients.

According to the National Institutes of Health, ALS is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement, such as chewing, walking and talking. ALS, sometimes called, Lou Gehrig’s disease, is progressive and incurable at this time. It is part of a wider group of disorders known as motor neuron diseases. The U.S. Centers for Disease Control and Prevention estimates between 14,000 to 15,000 Americans have ALS.

Tagged with:

About author

Related Articles