Age-related imbalance between synthesis and degradation of biomolecules in cells leads to the development of, among other, neurodegenerative diseases and diabetes. A decrease in autophagy, a process that is involved in degradation of damaged or dysfunctional cellular components, may contribute to this imbalance. Autophagy is regulated within cells through multiple signaling pathways, including the AMPK (AMP-activated protein kinase)-dependent pathway, which functions as a key sensor of changes in the cell's energy status. Researchers from the IBCh RAS, the A.N. Belozersky Institute of Physicochemical Biology of Moscow State University, the Patrice Lumumba Peoples' Friendship University of Russia, and other institutes assessed the ability of phenoxazine derivatives to activate this process. The lead compound demonstrated specific activation via the AMPK-dependent pathway and low cytotoxicity in three non-cancer cell lines. The work was published in Bioorganic Chemistry.

The staff of the Laboratory of Lipid Chemistry IBCh RAS, together with colleagues from Nizhny Novgorod State University and the Human Proteome Center of the Institute of Biomedical Chemistry, studied the effects of protein coronas formed in human blood plasma ex vivo on different liposomes carrying a colchicine analog. Today colchicine is considered as a possible treatment for cardiovascular complications. On a model of monocytes from human peripheral blood, the protein coronas have been shown to enhance the anti-inflammatory potential of liposomes. A particularly sharp effect was observed for liposomes bearing specific proteins, including minor ones in normal plasma.

A team of scientists from the Laboratory of Biomolecular NMR Spectroscopy at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, in collaboration with researchers from China, has made a breakthrough in understanding the function of Toll-like receptor 2 (TLR2), a key component of the innate immune system. Their study, published in FEBS Letters, reveals that TLR2 exhibits a previously unknown ability to bind zinc ions with high affinity and specificity. Toll-like receptors (TLRs) serve as the first line of defense in the immune system by recognizing pathogens and initiating immune responses. Despite extensive research, the precise molecular mechanisms governing TLR activation remain elusive. The newly identified zinc-binding capability of TLR2 provides fresh insights into its regulatory mechanisms. The researchers also identified specific amino acids essential for zinc coordination and TLR2 function, highlighting a potential link between zinc homeostasis and immune activation. These findings suggest that zinc plays a critical role in modulating TLR-mediated immune signaling, opening new avenues for research into immune system regulation and potential therapeutic applications.

A whole family of peptides with completely unexpected activity has been discovered in spider venom. These peptides inhibit mammalian purinergic receptors with high affinity and selectivity. A peptide called purotoxin-6 (PT6) from the venom of the crab spider Thomisus onustus inhibits P2X3 receptors, an important pharmacological target in a number of pain syndromes and chronic cough. PT6 has a compact fold and exhibits a potent analgesic effect in animal models of osteoarthritis and trigeminal neuralgia. At the same time, unlike small-molecule P2X3 ligands that are being developed as drugs, purotoxin does not cause dysgeusia, i.e., distortion of the sense of taste. Research on purotoxins began at the Institute of Bioorganic Chemistry some 20 years ago under the supervision of Academician Eugene Grishin and was successfully continued by Alexander Vassilevski. The results, unique on a global scale, were published in Molecular Therapy.

Potassium channels are one of the major players in the transduction of the nerve impulse, and mutations in their genes lead to neurological and cardiovascular diseases. The most important feature of K+-channels is their highest selectivity for K+ over Na+ and other cations. In the new work, members of the Group of in silico Analysis of Membrane Proteins Structure and the Laboratory of Molecular Instruments for Neurobiology analyzed all known 3D-structures of membrane proteins. As a result, the key principle of K+-channel selectivity filter architecture was confirmed: within it, oxygen atoms of the protein backbone are arranged in a chain of square antiprisms, replicating exactly the solvation geometry of the potassium ion. Distortion of the filter, for example during inactivation, is detected by the algorithm developed by the authors, which can be used for structural classification.

Preeclampsia is a serious pregnancy complication characterized by hypertension and multi-organ involvement in pregnant women. This condition occurs in 2–8% of all pregnancies and remains one of the leading causes of maternal and perinatal mortality. Despite decades of research, the exact mechanisms of its development are not fully understood, and existing therapeutic strategies remain only partially effective. A new study published by a team of Russian scientists led by Evgeny Knyazev, Polina Vishnyakova, Olga Lazareva, and Alexander Tonevitsky provides an overview of modern cellular models of preeclampsia and their potential in the search for new diagnostic and therapeutic approaches.

The International Society on Toxinology (IST) unites scientists and clinicians studying venoms, poisons, and toxins from all over the world. The society was founded in 1962. It organizes world and regional congresses, publishes the journal Toxicon, and sponsors the prestigious Redi Award.

A duplication of the chromosomal region 2q23.q23.2, carrying LYPD6 and LYPD6B genes, leads to intellectual disability and autistic features. Researchers from the Neurotransmitter and Neuroreceptor Bioengineering Laboratory, Shemyakin-Ovchnnikov Institute of Bioorganic Chemistry of RAS together with colleagues from Lomonosov State University and Institute for Biomedical Problems of RAS, used a mouse model to study the consequences of overexpression of the Lypd6 and Lypd6b proteins in the brain, which is typical for patients with autism and other neuropsychiatric disorders.

The application of the definition of taxonomic species to the description of evolutionary history of biological objects with chimeric genomes is a difficult task. The limited period of the existence of species and the lability of viral genomes can also make attempts to reconstruct the evolutionary history almost pointless. The processes of genetic exchange seem to be especially pronounced in temperate phages, but genetic rearrangements between evolutionarily close groups of phages can also affect φ29-like phages. However, we can try to plot the evolutionary traits of genes encoding separate essential proteins and their stable complexes.

Identifying high-affinity antibodies in human blood serum is a non-trivial task due to the extremely small number of circulating B-cells with the specified specificity. A team of scientists from the IBCh RAS proposed an effective approach that allows for the identification of high-affinity antibodies against pathogen proteins while simultaneously mapping epitopes, even in the absence of information about the structure of the pathogen's immunogens. To screen therapeutic antibodies in the blood of recovered donors, only the pathogen's transcriptome is needed to create a polypeptide library of antigens displayed on the surface of a bacteriophage. The work was published in the journal Communications Biology.