Researchers have discovered that a subunit of the ubiquitin-proteasome system acted independently of the proteasome machinery to regulate AMPA receptors, a type of glutamate receptor, at multiple steps of their life cycle. Published in the May 26, 2023, issue of Science, the findings could point to ways to target AMPA receptors. They are responsible for the majority of excitatory transmission in the central nervous system, and current drugs seeking to influence AMPA-based transmission are “good but they are not great,” Erin Schuman told BioWorld. “This regulatory particle is watching the glutamate receptor at each step.” Schuman is the director of the Max Planck Institute for Brain Research and the paper’s senior author.
Researchers have used cell culture experiments to understand how gene expression was affected in a patient with a rare pain insensitivity syndrome, and have identified a network of hundreds of genes whose expression was changed compared to sex-matched controls. Published online in the journal Brain on May 23, 2023, the research is one step toward translating a rare mutation into medications that could provide benefits for common ailments.
Long-term brain recordings from four patients with chronic pain have led investigators at the University of California at San Francisco to identify brain signals that could serve as biomarkers for each individual patients’ pain. The study, which was published online in Nature Neuroscience on May 22, 2023, demonstrated that “chronic pain can successfully be tracked, can successfully be predicted, in the real world while patients are ... going about their lives,” lead author Prasad Shirvalkar told reporters at a press conference announcing the findings. Shirvalkar is a neurologist at the University of California at San Francisco.
Long-term brain recordings from four patients with chronic pain have led investigators at the University of California at San Francisco to identify brain signals that could serve as biomarkers for each individual patients’ pain.
By analyzing gene expression patterns in the placenta of nearly 150 pregnancies and comparing them to fetal gene expression in the brain, researchers from the Lieber Institute for Brain Development have gained new insights into the importance of placental tissue in setting the risk trajectory for the development of schizophrenia. The work was published in Nature Communications on May 15, 2023.
Researchers have compared the cellular responses driving allergic asthma to those in individuals with allergic rhinitis and conjunctivitis but no allergic response in the lungs. Asthma is “an umbrella term,” Josalyn Cho told BioWorld. But under that umbrella, the largest group of people are those whose asthma begins in childhood. And “those folks almost exclusively develop their asthma after they develop allergies.”
Investigators have identified a second individual who remained cognitively normal into his late 60s despite having the PSEN1 E280A mutation, which causes a familial version of early-onset Alzheimer’s disease (AD). The likely source of protection, a mutation in a gene called Reelin, is distinct from the protective mechanism identified in the first case of an individual who was protected from the effects of PSEN1 E280A. That case was reported in 2019.
Swiss biopharma startup Aphaia Pharma AG is taking the concept of “location, location, location” to its extreme. The company started dosing patients in a phase II trial of its lead candidate, Aph-012, in late April, 2023. The trial is a randomized, double-blind, placebo-controlled, multicenter proof-of-concept study to evaluate Aph-012’s ability to improve glucose tolerance in individuals with prediabetes, as measured by a pathological oral glucose tolerance test. In another phase II trial, Aph-012 is being tested as a weight loss drug for individuals with a BMI between 30 and 40. Aph-012’s active ingredient? Glucose. But delivered exactly to the right place.
An experimental antibiotic was able to prevent recurrent Clostridioides difficile infections (rCDI) by killing bacterial spores as well as growing spores. Researchers from the University of Notre Dame reported their findings in the Proceedings of the National Academy of Sciences on May 8, 2023.
Blocking signaling through the ectodysplasin A2 receptor (EDA2R), a member of the TNF receptor family, protected tumor-bearing mice from developing muscle atrophy associated with cancer cachexia. Upstream and downstream of EDA2R, “we identified two distinct pathways and we demonstrated their involvement in muscle wasting,” Serkan Kir told BioWorld. Kir is a professor at the Koç University Center for Translational Medicine and corresponding author of the paper reporting the findings, which appeared in Nature on May 10, 2023.
