Breaking News
February 24, 2019 - Novel MRI sensor can peer deep into the brain to detect intracellular calcium activity
February 24, 2019 - AHA News: Diabetes Remains Dangerous Despite Modern Medicine
February 24, 2019 - Dup15q syndrome – Genetics Home Reference
February 24, 2019 - Could ‘Cardio-obstetrics’ curb rise in pregnancy-related deaths?
February 24, 2019 - Using computer model to visualize brain’s internal valuation system
February 24, 2019 - Study reveals insights into how the brain learns new locomotor patterns
February 24, 2019 - Depression Screening: MedlinePlus Lab Test Information
February 24, 2019 - Researchers discover a weakness in a rare cancer that could be exploited with drugs
February 23, 2019 - U.S.-based patient advocacy organizations received majority of pharma donations, finds study
February 23, 2019 - UCL and AIIMS collaborates to increase academic and student exchange
February 23, 2019 - Mechanism behind how diabetes causes muscle loss revealed
February 23, 2019 - Hepatocellular carcinoma diagnosis, prognosis and treatment may improve by identifying a protein
February 23, 2019 - The American Heart Association issues new reference toolkit for healthcare providers
February 23, 2019 - Studies explore physiological dangers that climate change will have on animal life
February 23, 2019 - Penn study reveals increase in health-related internet searches before ER visits
February 23, 2019 - Intensive therapy during early stages of MS leads to better long-term outcomes
February 23, 2019 - Prenatal Fluconazole Exposure Increases Neonatal Risks
February 23, 2019 - Mental Health Screening: MedlinePlus Lab Test Information
February 23, 2019 - Study suggests birth mechanics are part of the process that leads to autism
February 23, 2019 - Unhealthy diet linked to poor mental health
February 23, 2019 - Study gives a snapshot of crocodile evolution
February 23, 2019 - Research finds steep rise in self-poisonings among young people
February 23, 2019 - American Gastroenterological Association announces “AGA Future Leaders Program”
February 23, 2019 - Scientists uncover new mechanisms regulating neural stem cells
February 23, 2019 - Combinations of certain insecticides turn out to be lethal for honeybees
February 23, 2019 - AHA News: Why Are Black Women at Higher Risk of Dying From Pregnancy Complications?
February 23, 2019 - NIMH » Anxiety Disorders
February 23, 2019 - Autistic people urgently need access to tailored mental health support
February 23, 2019 - Newly designed molecule could benefit people with Friedrich’s Ataxia
February 23, 2019 - Chinese CRISPR twins may have better cognition and memory
February 23, 2019 - Study finds new genetic clues associated with asthma in African ancestry populations
February 23, 2019 - Fetal signaling pathways may offer future opportunities to treat lung damage
February 23, 2019 - Early-stage osteoarthritis drug wins prestigious innovation award
February 23, 2019 - Researchers report positive findings with dasotraline for ADHD in children ages 6-12
February 23, 2019 - News study reanalyzes the effects of noncaloric sweeteners on gut microbiota
February 23, 2019 - New device allows scientists to reproduce blow effects on the heart in lab
February 23, 2019 - Paying more attention to antibiotic dosing could improve clinical outcomes for CF patients
February 23, 2019 - Big-data analysis finds new link between popular arthritis drug and heart valve calcification
February 23, 2019 - Holy herb identified as a potential treatment for Alzheimer’s disease
February 23, 2019 - New technology platform digitally counts growth factors in single cells
February 23, 2019 - Physicians still remain at higher risk for burnout compared to other professionals
February 23, 2019 - Surgery and other treatments offer viable options for adult scoliosis
February 23, 2019 - Reduced antibody adaptability may make the elderly more vulnerable to influenza
February 23, 2019 - Researchers find increased rates of CRC screening in Kentucky after Medicaid expansion
February 23, 2019 - Neighborhood income, education associated with risk of disability progression in MS patients
February 23, 2019 - Endocrine Society opposes new rule that restricts access to Title X Family Planning Program
February 23, 2019 - 2019 guidelines for management of patients with atrial fibrillation
February 23, 2019 - Surprise rheumatoid arthritis discovery points to new treatment for joint inflammation
February 23, 2019 - A just-right fix for a tiny heart
February 23, 2019 - UMass Amherst scientist explores role of citrus peel in decreasing gut inflammation
February 23, 2019 - Owlstone Medical and Shanghai Renji Hospital collaborate to initiate breath biopsy lung cancer trial
February 23, 2019 - AMSBIO’s comprehensive portfolio of knock-out cell lines and lysates
February 23, 2019 - New app reliably determines physicians’ skills in forming accurate, efficient diagnoses
February 23, 2019 - Peripheral nerve injury can trigger the onset and spread of ALS, shows study
February 23, 2019 - Researchers uncover mechanisms that prevent tooth replacement in mice
February 23, 2019 - Once-a-day capsule offers new way to reduce symptoms of chronic breathlessness
February 23, 2019 - FDA Adds Boxed Warning for Increased Risk of Death with Gout Medicine Uloric (febuxostat)
February 23, 2019 - Phone-based intervention aids rheumatoid arthritis care
February 23, 2019 - Opioid epidemic makes eastern inroads and targets African-Americans
February 23, 2019 - New identified biomarker predicts patients who might benefit from HER2-targeted agents
February 23, 2019 - Study offers new insights into mechanisms of changes in erythrocytes under stress
February 23, 2019 - Antipsychotic polypharmacy may be beneficial for schizophrenia patients
February 23, 2019 - Researchers investigate how marijuana and tobacco co-use affects quit attempts by smokers
February 23, 2019 - Patients with diabetes mellitus have high risk of stable ischemic heart disease
February 23, 2019 - Transparency on healthcare prices played key role in Arizona health system’s turnaround
February 23, 2019 - A comprehensive, multinational review of peppers around the world
February 23, 2019 - Study finds modest decrease in burnout among physicians
February 23, 2019 - A simple change can drastically reduce unnecessary tests for urinary tract infections
February 23, 2019 - Deep Learning-Enhanced Device Detects Diabetic Retinopathy
February 23, 2019 - Researchers discover new binding partner for amyloid precursor protein
February 23, 2019 - Modest decrease seen in burnout among physicians, researchers say | News Center
February 23, 2019 - Transplanting bone marrow of young mice into old mice prevents cognitive decline
February 23, 2019 - Mogrify to accelerate novel IP and cell therapies using $3.7m USD funding
February 23, 2019 - Johns Hopkins study describes cells that may help speed bone repair
February 23, 2019 - Scientists demonstrate influence of food odors on proteostasis
February 23, 2019 - Researchers unlock the secret behind reproduction of fish called ‘Mary’
February 23, 2019 - Acupuncture Could Help Ease Menopausal Symptoms
February 23, 2019 - Researchers use AI to detect early signs of Alzheimer’s
February 23, 2019 - On recovery, vulnerability and ritual: An exhibit in white | News Center
February 23, 2019 - Memory Stored in Unexpected Region of the Brain
Researchers discover new promising target point for cancer and diabetes therapies

Researchers discover new promising target point for cancer and diabetes therapies

image_pdfDownload PDFimage_print

If certain signaling cascades are misregulated, diseases like cancer, obesity and diabetes may occur. A mechanism recently discovered by scientists at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin and at the University of Geneva has a crucial influence on such signaling cascades and may be an important key for the future development of therapies against these diseases. The results of the study have just been published in the prestigious scientific journal Molecular Cell.

Cell growth and cell differentiation as well as the release and efficacy of hormones such as insulin depend on the presence of lipids. Lipids are small molecules resembling fat. They are the building blocks of cell membranes, and they also serve as molecular switches in signaling cascades. Such cascades play a crucial role in the control of cell growth and division as well as in differentiation processes such as the formation of new blood vessels referred to as angiogenesis. If signaling cascades are disturbed, diseases such as cancer or metabolic disorders such as obesity and diabetes can occur. The ability to influence the enzymes involved in the biosynthesis of signaling lipids in cells could thus serve as a starting point for the treatment of these diseases.

The team around Professor Dr. Volker Haucke at the FMP pursued this approach: Years of work allowed the team to successfully express and purify the lipid kinase PI3KC2A and to analyze the enzyme in detail. The PI3KC2A kinase enzyme performs crucial functions in receptor uptake, cell division, the release of and signaling by insulin, and in angiogenesis. Together with Dr. Oscar Vadas of the University of Geneva, the FMP Team performed intricate studies on the structural biology and cell biology of the kinase. Their studies revealed an initially inactive, auto-inhibited form of the PI3KC2A kinase in the cytoplasm of cells. External signals can then activate the kinase as it becomes recruited to the cell membrane. Such signaling cascades are initiated by the docking of protein ligands such as insulin or growth factors to receptors in the cell membrane. The ligand-bound receptors become activated and transmit signals into the cell interior. This receptor signaling process is accompanied by the invagination of the cell membrane to eventually form vesicles that deliver the active membrane-bound receptor into the cytoplasm. Lipid kinases such as PI3KC2A participate in the process of vesicle formation and in the signaling cascades inside the cell.

For the first time, the team of scientists was able to observe the transition of PI3KC2A from the inactive into an active form. Dr. Oscar Vadas describes this mechanism: “In its inactive form, the kinase exists rolled up looking as if it had wrapped its ‘arms’ around itself. In order to activate the kinase, two specific components of the cell membrane have to be in the same location at the same time. When this happens, the kinase unfolds its ‘arms’, and each ‘arm’ binds to one of the two components”. The activated kinase within seconds synthesizes many signaling lipid molecules. In turn, these signaling lipids control the uptake of activated signaling receptors into the cell (image) and thereby regulate processes such as cell growth, division and differentiation.

These findings are of great importance for basic research as the Berlin/Geneva team has provided unprecedented molecular insight into the central cellular process of receptor uptake. Moreover, the scientific work presents a major leap toward the pharmacological manipulation of PI3KC2A and related kinases. “For the first time, we have a handle on a mechanism, which may eventually enable us to alter PI3KC2A lipid kinase activity. This may provide a direct target for therapies”, emphasizes Professor Dr. Volker Haucke. For example, small molecules that block PI3KC2A activity could serve as anti-tumor agents given that angiogenesis is important for nutrient supply to tumors. As studies with mice suggest, the pharmacological inhibition of PI3KC2A activity should bring angiogenesis to a stop. The FMP scientists in Berlin are now looking for such agents.

“We have discovered a new promising target and are keen to further explore its therapeutic potential”, promises Professor Dr. Volker Haucke referring to the initiated compound search. While the FMP does not develop drugs itself, the institute aims to provide new leads for future drug development. Professor Haucke is confident: “In this case, we expect to identify candidate molecules that may at some point in the future become clinically useful.”

Source:

http://www.leibniz-fmp.de/press-media/press-releases/press-releases-single-view1/article/a-molecular-switch-may-serve-as-new-target-point-for-cancer-and-diabetes-therapies.html

Tagged with:

About author

Related Articles