Breaking News
November 16, 2018 - Scientist Dr David Taylor of MR Solutions is a finalist in the BMW i UK Tech Founder Awards
November 16, 2018 - Earlier treatment could help reverse autistic-like behavior in tuberous sclerosis
November 16, 2018 - Vegetables and salad may include bacteria that are resistant to antibiotics
November 16, 2018 - Endocrine Society chooses four Diabetes Caucus leaders as winners of Diabetes Champion Award
November 16, 2018 - Brain and muscle cells found within kidney organoids
November 16, 2018 - Person’s sex hormones may play key role in trauma survival, finds study
November 16, 2018 - PTEN Genetic Test: MedlinePlus Lab Test Information
November 16, 2018 - Toxic metal pollution linked with development of autism spectrum disorder
November 16, 2018 - Calcified nodules in the retina increase risk for progression to late stages of AMD
November 16, 2018 - ZEISS teams up with arivis AG to offer complete 3D imaging solutions
November 16, 2018 - Georgia State professor receives $1.2 million grant to study how the brain controls eating behavior
November 16, 2018 - Specific bacterial toxins reduce number of cells suppressing immune response
November 16, 2018 - Review by ID physician improves outcomes for outpatient parenteral antimicrobial therapy
November 16, 2018 - Conditions that produce signs similar to arthritis
November 16, 2018 - AHA: Dapagliflozin Noninferior to Placebo for MACE in T2DM
November 16, 2018 - Surgery remains best treatment for appendicitis, Stanford study finds
November 16, 2018 - Non-surgical fistula creation system Ellipsys becomes key focus of attention at CiDA
November 16, 2018 - Researchers find no link between ‘allergy friendly’ dogs and lower risk of asthma
November 16, 2018 - Researchers elucidate new rules of connectivity of neurons in the neocortex
November 16, 2018 - Treating children with ‘bubble baby disease’
November 16, 2018 - Nexus announces availability of Arsenic Trioxide Injection in the US
November 16, 2018 - Researchers find metabolite shuttle between cells in the liver that may combat tissue fibrosis
November 16, 2018 - AHA: PTSD Common Among Those Who Suffer Tear in the Aorta’s Wall
November 16, 2018 - Many RA patients’ pain related to central nervous system
November 16, 2018 - Changes in Himalayan gut microbiomes linked to diet
November 16, 2018 - Inhibition of prostaglandin E2 enhances ability to combat infectious colitis
November 16, 2018 - Chronic dry eye can slow reading rate and disrupt day to day tasks
November 16, 2018 - Researchers develop new drug molecule that inhibits inflammation
November 16, 2018 - Dementia symptoms peak in winter and spring, study finds
November 16, 2018 - Stanford tobacco researcher weighs in on JUUL
November 16, 2018 - Increasing omega-3 fatty acid intake during pregnancy reduces risk of premature birth, review finds
November 16, 2018 - Researchers find no link between infants waking up at night and later developmental problems
November 16, 2018 - Both parents and children agree about confidential medical services
November 16, 2018 - FDA warns against use of unapproved pain medications with implanted pumps
November 16, 2018 - Precision medicine-based approach to slow or reverse biologic drivers of Alzheimer’s disease
November 16, 2018 - Study provides new insight into norovirus outbreaks, may help guide efforts to develop vaccines
November 16, 2018 - Inexpensive, portable air purifier could help protect the heart from pollution
November 16, 2018 - New 15-minute scan could help diagnose brain damage in babies up to two years old
November 16, 2018 - Deep brain stimulation not effective for treating early Alzheimer’s
November 16, 2018 - Traditional chemotherapy superior to new alternative for oropharyngeal cancers | News Center
November 16, 2018 - What This Pond Protist Does With Its Genome Will Astound You
November 15, 2018 - Researchers develop tool that speeds up analysis and publication of biomedical data
November 15, 2018 - Scientists identify mechanism used by lung cancer cells to obtain glucose
November 15, 2018 - Abnormalities in development of the brain could be involved in onset of autism, finds new study
November 15, 2018 - Soy protein equally effective as animal protein in building muscle strength
November 15, 2018 - American Academy of Pediatrics, Nov. 2-6
November 15, 2018 - Dopamine drives early addiction to heroin
November 15, 2018 - Variance in gut microbiome in Himalayan populations linked to dietary lifestyle | News Center
November 15, 2018 - Reducing Cardiovascular Disease: The Amish Way
November 15, 2018 - King’s researchers launch charter to guide organizations to engage abuse survivors in research
November 15, 2018 - Enable Injections enters into development agreements with UCB and Apellis Pharmaceuticals
November 15, 2018 - TGen North collaborates with NARBHA Institute to advance human health
November 15, 2018 - Researchers discover molecular basis for therapeutic actions of an African folk medicine
November 15, 2018 - Human Cell Atlas study of early pregnancy shows how mother’s immune system is modified
November 15, 2018 - New guidelines for detecting and managing sarcopenia to be launched in the UK
November 15, 2018 - Researchers explore role of dietary composition on energy expenditure
November 15, 2018 - Elsevier launches Entellect™ Platform, unlocking value by creating AI-ready life sciences data
November 15, 2018 - Now that cannabis is legal in Canada, let’s use it to tackle the opioid crisis
November 15, 2018 - In the Spotlight: At the intersection of tech, health, and ethics
November 15, 2018 - Traditional Glaucoma Test Can Miss Severity of the Disease
November 15, 2018 - Researchers directly connect activities of genes with instinctive behavior in male cichlids
November 15, 2018 - Salk researchers report new methods to identify AD drug candidates with anti-aging properties
November 15, 2018 - St. Jude Hospital announces availability of largest collections of leukemia samples
November 15, 2018 - Attenua Announces First Patient Treated in Phase 2 Clinical Trial in Chronic Cough with Bradanicline
November 15, 2018 - Designing a novel cell-permeable peptide chimera to promote wound healing
November 15, 2018 - NEI investigators combine two imaging modalities to view the retina in unprecedented detail
November 15, 2018 - Determining how hearts develop to better understand congenital heart defects
November 15, 2018 - Maverick immune cells can act independently to identify and kill cancer cells, finds research
November 15, 2018 - Advanced AI and big data methods to tackle dementia
November 15, 2018 - Report reveals increase in pancreatic cancer death rates across Europe
November 15, 2018 - Luxia Scientific announces availability of its gut microbiome test in Luxembourg
November 15, 2018 - New diabetes drugs linked to increased risk of lower-limb amputation and ketoacidosis
November 15, 2018 - New approach targets matrix surrounding neurons to protect neurons after stroke
November 15, 2018 - Lilly Submits New Drug Application to the FDA for Lasmiditan for Acute Treatment of Migraine
November 15, 2018 - Heart failure patients shouldn’t stop meds even if condition improves: study
November 15, 2018 - Parents and carers of people with diabetes experience emotional or mental health problems
November 15, 2018 - RetiPharma secures funding to develop new peptide drug for treating degenerative eye disorders
November 15, 2018 - Breakthrough research could lead to a new wave of cancer-fighting antibodies
November 15, 2018 - Mylan and Biocon launch new insulin glargine biosimilar in the UK
November 15, 2018 - For wildfire safety, only particular masks guard against toxic particulate matter
Findings offer new insight into early changes that occur during AD pathology

Findings offer new insight into early changes that occur during AD pathology

image_pdfDownload PDFimage_print

Alzheimer’s disease (AD) is the most common form of dementia, involving memory loss and a reduction in cognitive abilities. Patients with AD develop multiple abnormal protein structures in their brains that are thought to destroy or damage nerve cells (neurons). One of these structures, the senile plaque, is made up of clumps of beta-amyloid (Aβ) peptide which form in the spaces between neurons.

Many advanced clinical trials in patients with AD have attempted to slow down or reverse the disease by targeting these plaques for removal. However, despite the successful decrease in Aβ aggregation, these trials mostly have failed to improve memory or cognitive function in AD patients.

Before the formation of Aβ aggregates, studies revealed changes in the phosphorylation (a chemical modification) of certain proteins, including SRRM2. This protein was thought to be involved in a form of gene regulation known as splicing, but its exact function was unclear.

Now, a Japanese team of researchers led by Tokyo Medical and Dental University (TMDU) has examined levels of SRRM2 phosphorylation in a mouse model of AD, and found that they increased prior to Aβ aggregation. This ultimately prevented the nuclear transport of SRRM2 and led to reduced levels of PQBP1 protein, which has been linked with the neurodevelopmental and intellectual disorders. The study results were reported in Molecular Psychiatry.

“We showed that the increased phosphorylation of SRRM2 prevented it from interacting with another protein which aids protein folding,” says first author Hikari Tanaka. “In the absence of this interaction, SRRM2 remained unfolded so was not transported to the nucleus and was degraded in the cytoplasm.”

The team next measured levels of SRRM2 and PQBP1 protein in the cerebral cortex of early-phase AD mice and human end-stage AD patients as well as in human AD iPS cells. Both proteins were greatly reduced compared with corresponding amounts in healthy controls.

“To find out what effect a reduction in PQBP1 would have in vivo, we generated knockout mice in which the PQBP1 gene was disrupted,” explains corresponding author Hitoshi Okazawa. “We observed cognitive decline and changes in the morphology of their synapses, which are junctions between neurons that allow electrical and chemical communication. These changes were caused by disrupted patterns of synapse gene splicing.”

A viral vector containing PQBP1 was used to recover the synapse protein expression in these mice. Not only did this restore PQBP1 expression, but it also recovered the abnormal phenotypes. These findings offer a new insight into early changes that occur during AD pathology involving splicing proteins, suggesting possibilities for gene therapies by virus vectors.

Source:

http://www.tmd.ac.jp/english/press-release/20181011_1/index.html

Tagged with:

About author

Related Articles