PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

„Fat jam" in the cell

New insights into the brain disease "Niemann-Pick type C"

2021-02-24
(Press-News.org) In the journal Nature Communications, scientists of the German Center for Neurodegenerative Diseases (DZNE) report new findings on the mechanisms of "Niemann-Pick type C disease" (NPC). This rare brain disorder mainly manifests in childhood and includes severe neurological and psychiatric symptoms. Researchers led by Dr. Sabina Tahirovic have now found evidence that already at an early stage, NPC is associated with neuroinflammation and that this condition is triggered by impaired intracellular lipid transport. In addition, they identified pathological features in the blood of affected individuals that in the future could assist to better monitor the course of the disease and response to therapy.

NPC is a hereditary metabolic disorder and among the rare diseases. In Germany, it is estimated to affect several hundred people. In these individuals, fat molecules - known as lipids - accumulate in their brains and other organs such as the liver. The consequences are severe: ranging from psychoses, epileptic seizures, disturbances in movement and coordination to cognitive impairments and dementia. "NPC mainly manifests in childhood," said Dr. Sabina Tahirovic, a research group leader at the DZNE's Munich site. "Current therapies can alleviate symptoms somewhat, but cannot sustainably halt progression of the disease. Many patients affected by NPC die before they reach adulthood."

Early Inflammations

NPC is caused by defects in one of two genes: NPC1 and NPC2. Both are essential for the lipid recycling and the brain is particularly sensitive to such defects. In NPC, brain cells become overloaded with cholesterol and other lipids, leading to dysfunctions and, in the long term, to the death of neurons. The immune cells of the brain, the microglia, are also affected by the disease. Microglia trigger inflammatory processes; experts refer to this as "neuroinflammation". "Until now, the reaction of microglia was considered to happen at late disease stages. We have now found that neuroinflammation occurs ahead of neuronal loss," Tahirovic explained. "Thus, the inflammatory processes are not necessarily a response to neuronal damage, as anticipated. Inflammation starts before and appears to contribute to the disease progression." The findings of Tahirovic's team are based on studies in mice with defective NPC1 gene. Noteworthy, in humans, about 95 percent of NPC cases are due to flaws in this gene.

Out of Control

Microglia have a protective function that includes clearing cellular junk out of the way. However, the Munich scientists found that the immune cells behaved overly aggressively. "The microglia seemed out of control and more likely to do harm than good. In our experiments, they showed a tendency to over-ambitiously inhale cellular material," Tahirovic said. In their search for the causes of this misbehavior, the researchers took a closer look at the processes inside the cells: with surprising results. "Until now, it has been assumed that the accumulation of lipids in NPC impairs the degradation machinery. However, our studies point to transport problems. This means that the lipids could well be degraded, but on the way there, they get stuck in a molecular traffic jam," said the Munich researcher.

Blood Samples from Patients

In addition to these studies in mice, Tahirovic's team also examined blood samples from patients with NPC. Thanks to a collaboration with the Department of Neurology at the Ludwig-Maximilians-Universität München, the researchers were able to analyze blood from a total of seven patients. "This is quite a large number because NPC is so rare," Tahirovic pointed out. "Human microglia are difficult to access, this would require taking brain tissue. That's why we looked at white blood cells. Specifically at so-called macrophages, they are close relatives to microglia."

Potential Biomarkers

Indeed, numerous similarities were found between the macrophages of patients and the microglia of mice with NPC-like pathology - both in terms of molecular features and aggressive phagocytic behavior. "The macrophages appear to mirror key features of microglia. If they also respond in a similar way as microglia to therapies, they might be useful as biomarkers," Tahirovic said. "This would expand the existing toolkit. Because presently, monitoring disease progression of NPC and response to treatments is essentially limited to observing clinical symptoms."

Combined Therapies

Current approaches to treating NPC aim to reduce the amount of lipids in the cells. "Generally, this makes sense, because lipid overload is triggering the disease. However, our results emphasize the relevance of inflammatory processes. Insofar, the combination of lipid reduction and modulation of the immune response should also be considered in therapy development," said Tahirovic.

INFORMATION:

Original Publication Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia, Alessio Colombo et al., Nature Communications (2021), DOI: 10.1038/s41467-021-21428-5

On the German Center for Neurodegenerative Diseases (DZNE) The DZNE investigates all aspects of neurodegenerative diseases (such as Alzheimer's and Parkinson's and Amyotrophic lateral sclerosis) in order to develop novel approaches of prevention, treatment, and health care. The DZNE is comprised of ten sites across Germany and cooperates closely with universities, university hospitals, and other institutions on a national and international level. The DZNE is a member of the Helmholtz Association.
Website: http://www.dzne.de/en



ELSE PRESS RELEASES FROM THIS DATE:

One in five people in south London live with multiple long-term conditions

2021-02-24
New research has found one in five people in the south London live with multimorbidity. The study, published today in the Lancet Regional Health by researchers from King's College London and the NIHR Guy's and St Thomas' Biomedical Research Centre and supported by Impact on Urban Health, examined the prevalence of multimorbidity - two or more long-term diseases at once - and identified key relationships between diseases. Researchers analysed electronic health records from participants aged 18 and over between April 2005 and May 2020 in one London borough. The borough has a deprived, ...

Machine learning tool can predict malignancy in patients with multiple pulmonary nodules

2021-02-24
PHILADELPHIA - A machine learning-based tool was able to predict the risk of malignancy among patients presenting with multiple pulmonary nodules and outperformed human experts, previously validated mathematical models, and a previously established artificial intelligence tool, according to results published in Clinical Cancer Research, a journal of the American Association for Cancer Research. Tools currently available can predict malignancy in patients with single nodules; predictive tools for patients presenting with multiple nodules are limited. "With the adoption of widespread use of thoracic computed tomography (CT) for lung cancer screening, the detection of multiple pulmonary nodules has become increasingly ...

Self-monitoring using digital health tools is associated with weight loss

2021-02-24
SILVER SPRING, Md.--A systematic review of multiple randomized controlled studies among adults with overweight or obesity showed that greater engagement in self-monitoring using digital health tools was associated with significant weight loss, according to a paper published online in Obesity, The Obesity Society's flagship journal. This is the first comprehensive systematic review to examine the relationship between digital self-monitoring and weight loss. "Digital health tools have flourished in the past decade," said Michele L. Patel, PhD, post-doctoral ...

Red light put moths in the mood

Red light put moths in the mood
2021-02-24
Do you dim the lighting and turn on the red light for a romantic night in with your partner? It turns out moths aren't so different in that regard. A new study published in END ...

Mangrove forests store more carbon when they're more diverse

Mangrove forests store more carbon when theyre more diverse
2021-02-24
Mangrove forests with greater species diversity can store more carbon, according to new research published in the British Ecological Society journal Functional Ecology. Researchers studying mangrove forests in Hainan Island, China, have found that species diversity in mangrove forests enhances both biomass production (the quantity of organic matter) and soil carbon storage. The findings highlight the impotence of conserving mangrove biodiversity as a nature-based solution to mitigate climate change. The East side of the island was found to have the highest mangrove biomass, diversity and carbon storage, with a mean of 537 tonnes of carbon per hectare (Mg C ha-1). ...

Vaginal pessaries prove effective in treating pelvic organ prolapse long-term

2021-02-24
CLEVELAND, Ohio (Feb 24, 2021)--The aging population combined with increasing obesity rates has resulted in more women experiencing pelvic organ prolapse. Common treatment options include pelvic reconstructive surgery or the use of pessaries to prop up descending organs. A new study evaluated the long-term effectiveness of pessaries, as well as reasons why women discontinued their use. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS). Despite the fact that vaginal pessaries have existed in some form for thousands of years to help treat pelvic organ prolapse, few studies have been published regarding their long-term use and effectiveness. Pessaries are devices inserted into the vagina ...

Buckyballs on DNA for harvesting light

2021-02-24
Organic molecules that capture photons and convert these into electricity have important applications for producing green energy. Light-harvesting complexes need two semiconductors, an electron donor and an acceptor. How well they work is measured by their quantum efficiency, the rate by which photons are converted into electron-hole pairs. Quantum efficiency is lower than optimal if there is "self-quenching", where one molecule excited by an incoming photon donates some of its energy to an identical non-excited molecule, yielding two molecules at an intermediate energy state too low ...

Ancestry estimation perpetuates racism, white supremacy

2021-02-24
BINGHAMTON, NY -- Ancestry estimation -- a method used by forensic anthropologists to determine ancestral origin by analyzing bone structures -- is rooted in "race science" and perpetuates white supremacy, according to a new paper by a forensic anthropologist at Binghamton University, State University of New York. By themselves, bones seem somewhat uniform to the untrained eye. They lack the traits we so often use to categorize fellow humans: hair texture, the shape of nose and eye, skin pigmentation. Forensic anthropologists know that race isn't based in biological fact, but in a history and culture that assigns meaning to physical traits that occur among different ...

Measuring carbon nanotubes taken up by plants

Measuring carbon nanotubes taken up by plants
2021-02-24
Carbon nanotubes are tiny. They can be a hundred thousand times smaller than the width of a human hair. But they have huge potential. Products manufactured using carbon nanotubes include rebar for concrete, sporting goods, wind turbines, and lithium batteries, among others. Potential uses of carbon nanotubes could extend to diverse fields, such as agriculture, biomedicine and space science. But as we use more carbon nanotubes to make things, we also increase the chances that these nanotubes enter different environments and ecosystems. "That makes it important to understand how ...

Mushrooms add important nutrients when included in the typical diet

Mushrooms add important nutrients when included  in the typical diet
2021-02-24
February 24, 2021 - The second study published in as many months has identified another reason to add more mushrooms to the recommended American diet. The new research , published in Food & Nutrition Research (February 2021), examined the addition of mushrooms to U.S. Department of Agriculture (USDA) Food Patterns resulting in the increase of several micronutrients including shortfall nutrients, while having a minimal to zero impact on overall calories, sodium or saturated fat. Dr. Victor L. Fulgoni III and Dr. Sanjiv Agarwal looked at the nutritional ...

LAST 30 PRESS RELEASES:

Program takes aim at drinking, unsafe sex, and sexual assault on college campuses

Inability to pay for healthcare reaches record high in U.S.

Science ‘storytelling’ urgently needed amid climate and biodiversity crisis

KAIST Develops Retinal Therapy to Restore Lost Vision​

Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response

Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid

Low LDL cholesterol levels linked to reduced risk of dementia

Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients

Almost one in ten people surveyed report having been harmed by the NHS in the last three years

Enhancing light control with complex frequency excitations

New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients

New insight into factors associated with a common disease among dogs and humans

Illuminating single atoms for sustainable propylene production

New study finds Rocky Mountain snow contamination

Study examines lactation in critically ill patients

UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award

Doubling down on metasurfaces

New Cedars-Sinai study shows how specialized diet can improve gut disorders

Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana

PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation

ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy

How VR technology is changing the game for Alzheimer’s disease

A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet

Balance between two competing nerve proteins deters symptoms of autism in mice

Use of antifungals in agriculture may increase resistance in an infectious yeast

Awareness grows of cancer risk from alcohol consumption, survey finds

The experts that can outsmart optical illusions

Pregnancy may reduce long COVID risk

Scientists uncover novel immune mechanism in wheat tandem kinase

Three University of Virginia Engineering faculty elected as AAAS Fellows

[Press-News.org] „Fat jam" in the cell
New insights into the brain disease "Niemann-Pick type C"