Nav: Home

A new therapeutic target against diseases caused by lipid accumulation in cells

December 02, 2019

Researchers from the University of Barcelona (UB) and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) found a new molecular mechanism involved in the regulation of the cholesterol movement in cells, an essential process for a proper cell functioning.

The study, published in the journal Cellular and Molecular Life Sciences, also identifies the protein Annexin A6 (AnxA6) as a key factor in this regulation and as a potential therapeutical target against diseases that are caused by the accumulation of cholesterol and other lipids in endosomes, such as the Niemann-Pick disease type C1, a minority genetic disease with no cure that causes hepatic damage and a type of dementia.

The study is led by Carles Enrich and Carles Rentero, lecturers at the unit of Cell Biology in the Department of Biomedicine of the Faculty of Medicine and Health Sciences at the UB and the CELLEX Biomedical Research Center (IDIBAPS-UB). This is the result of six years of research and a collaboration with Thomas Grewal, from the University of Sydney; Elina Ikonen, from the University of Helsinki, and the research group on Lipids and Cardiovascular Pathology of the Biomedical Research Institute at Hospital Sant Pau.

Study with the CRISPR/Cas9 editing technology

Cholesterol is essential in the organization of membranes and it also modulates the vesicular trafficking, basic mechanisms for the cell functioning. To coordinate and regulate the balance, or homeostasis in cholesterol, cells have developed a molecular machinery, which is not fully understood yet. "The understanding of these mechanisms is very important to treat diseases in which there is an accumulation of cholesterol and other lipids which cause serious physiological alterations in the liver, spleen and especially the nervous system", note Carles Enrich and Carles Rentero.

One of such diseases is Niemann-Pick type C1, caused by a mutation in the NPC1 gene, which causes the accumulation of cholesterol in the cell interior of the endosome. In order to study this mechanism, researchers used the CRISPR/Cas9 genetic editing technique to block a molecule -AnxA6 protein- in cells with the phenotype of the disease. The effect of such block resulted in the release of the endosome cholesterol, showing the essential role of this protein in the regulation of cholesterol transfer.

Increasing membrane contact sites

The results of the study also show this release occurred thanks to a significant increase of membrane contact sites (MCS), nanometric structures that can be seen through electronic microscopy. According to the authors, these membrane contact sites are just a few inside the cells of the affected patients, therefore, silencing AnxA6 induces the creation of MCS, stops the effect of the NPC1 gene mutation and redirects cholesterol towards other cell compartments, returning to cell normality.

"Results could help treating the clinical impact of the accumulation of cholesterol in Niemann-Pick and about twelve more diseases, among which are different types of cancer (pancreas, prostate, breast), in which the lipidic metabolism plays a fundamental role", note the researchers.

A new paradigm in the study of the cholesterol cell transport

The membrane contact sites being involved in the cholesterol transport is a pioneering result in this field, since researchers thought -so far- that lipid transport was carried out through vesicles and a type of specialized proteins. "We do not know much about the functioning and dynamics of membrane contact sites, but this study goes together with recent ones and shows MCS are a new paradigm for the understanding of the regulation, transport and homeostasis of lipids, cholesterol and calcium", conclude the researchers.

University of Barcelona

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Our Relationship With Water
We need water to live. But with rising seas and so many lacking clean water – water is in crisis and so are we. This hour, TED speakers explore ideas around restoring our relationship with water. Guests on the show include legal scholar Kelsey Leonard, artist LaToya Ruby Frazier, and community organizer Colette Pichon Battle.
Now Playing: Science for the People

#569 Facing Fear
What do you fear? I mean really fear? Well, ok, maybe right now that's tough. We're living in a new age and definition of fear. But what do we do about it? Eva Holland has faced her fears, including trauma and phobia. She lived to tell the tale and write a book: "Nerve: Adventures in the Science of Fear".
Now Playing: Radiolab

First things first: our very own Latif Nasser has an exciting new show on Netflix. He talks to Jad about the hidden forces of the world that connect us all. Then, with an eye on the upcoming election, we take a look back: at two pieces from More Perfect Season 3 about Constitutional amendments that determine who gets to vote. Former Radiolab producer Julia Longoria takes us to Washington, D.C. The capital is at the heart of our democracy, but it's not a state, and it wasn't until the 23rd Amendment that its people got the right to vote for president. But that still left DC without full representation in Congress; D.C. sends a "non-voting delegate" to the House. Julia profiles that delegate, Congresswoman Eleanor Holmes Norton, and her unique approach to fighting for power in a virtually powerless role. Second, Radiolab producer Sarah Qari looks at a current fight to lower the US voting age to 16 that harkens back to the fight for the 26th Amendment in the 1960s. Eighteen-year-olds at the time argued that if they were old enough to be drafted to fight in the War, they were old enough to have a voice in our democracy. But what about today, when even younger Americans are finding themselves at the center of national political debates? Does it mean we should lower the voting age even further? This episode was reported and produced by Julia Longoria and Sarah Qari. Check out Latif Nasser's new Netflix show Connected here. Support Radiolab today at