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Том 90, № 11 (2025)
Articles
Andrey Nikolaevich Belozersky: Five Decades in Science. Preface to the Special Issue
Biochemistry. 2025;90(11):1539–1543
1539–1543
LABORATORY EVOLUTION: MOLECULAR GENETIC BASIS AND PHENOTYPIC PLASTICITY
Аннотация
Adaptive laboratory evolution (ALE) is a scientific approach that aims to study the molecular basis of adaptation. It is a widely used tool that facilitates a deeper understanding of the genetic and/or metabolic pathways of evolution. One of the primary objectives of experimental evolution is to predict which mutations are the "significant" drivers of adaptation. The use of re-sequencing of the entire genome facilitates the identification of mutations that occurred during ALE, and consequently, the biochemical changes that occurred with the experimental lines. In addition to its theoretical aspects, ALE also has a practical side. It represents an innovative approach to creating evolved strains of microbes with desired characteristics, such as rapid growth, stress resistance, efficient use of various substrates, and the production of products with sufficiently high added value (amino acids, ethanol, aromatic compounds, lipids). The review presents the results of studies explaining and demonstrating the relationship of mutations with the observed phenotypic and biochemical changes, as well as the possibilities of microorganisms as model objects for conducting laboratory evolutionary experiments and testing various evolutionary hypotheses. The objective of this study was to emphasize the accomplishments attained by virtue of the ALE strategy, whilst concomitantly highlighting outstanding concerns and the unresolved limitations of the method.
Biochemistry. 2025;90(11):1544-1560
1544-1560
DNA DOUBLE-STRAND BREAK REPAIR PATHWAYS AND THEIR ROLE IN CHROMOSOMAL ABERRATION
Аннотация
Double-strand break repair pathways differ in their ability to prevent errors during the joining of broken DNA ends. When DNA breaks on different chromosomes are joined, translocations can form, potentially leading to tumor development. This review discusses the main mechanisms of double-strand break (DSB) repair and the factors that influence the repair process and the formation of chromosomal rearrangements in human cells.
Biochemistry. 2025;90(11):1561-1578
1561-1578
CIRCULATING TUMOR DNA AND THE EVALUATION OF THE EFFICACY OF NEOADJUVANT DRUG THERAPY IN BREAST CANCER PATIENTS
Аннотация
The main characteristics of circulating tumor DNA (ctDNA) and features of its analysis are described in the review. ctDNA constitutes a small part of the cell-free DNA in cancer patients. ctDNA is currently considered as a promising marker for assessing the effectiveness of treatment, prognosis and monitoring of oncological diseases, including breast cancer (BC). A plenty of patients with BC today receive neoadjuvant therapy, the effectiveness of which determines the necessity and volume of further drug treatment. The most sensitive method for assessing the effect of neoadjuvant drug therapy may be the determination of ctDNA. ctDNA analysis provides regular dynamic monitoring of molecular changes during treatment, predicts response to neoadjuvant drug therapy and the risk of disease relapse. This method can become an additional tool for personalized therapy of BC.
Biochemistry. 2025;90(11):1579–1600
1579–1600
In vivo AND in vitro MODELS OF HEPATITIS B VIRUS INFECTION
Аннотация
Hepatitis B virus (HBV) is a hepatotropic virus from the Hepadnaviridae family and the causative agent of acute and chronic hepatitis B (CHB). The outcomes of HBV infection include liver cirrhosis and hepatocellular carcinoma (HCC), posing a significant burden on healthcare systems worldwide. In the nuclei of infected hepatocytes of patients with CHB, the HBV genome persists as a pool of covalently closed circular DNA (cccDNA) molecules. Current therapeutic strategies cannot directly target cccDNA. Instead, available treatments focus on long-term suppression of viral replication and require lifelong administration. The development and evaluation of novel antiviral agents capable of achieving complete HBV eradication require relevant in vivo and in vitro models of HBV infection. Among the available animal models, the following categories can be distinguished: (1) animals naturally susceptible to HBV; (2) surrogate models employing species susceptible to related hepadnaviruses; (3) non-susceptible animals receiving the HBV genome via recombinant viral vectors; (4) models utilizing human hepatocyte xenografts. Among the available in vitro models, primary human and treeshrew (Tupala) hepatocytes fully support the HBV replication cycle, but they rapidly lose susceptibility to the virus. In turn, human hepatoma cell lines are not directly susceptible to HBV, but support viral replication upon transfection with the viral genome. This review discusses the key characteristics, advantages, limitations and areas of application of currently available in vivo and in vitro models of HBV infection.
Biochemistry. 2025;90(11):1601-1620
1601-1620
METHODOLOGICAL TOOLBOX FOR DETECTION AND RESEARCH OF MICROPEPTIDES: FROM GENOME TO FUNCTION
Аннотация
Micropeptides encoded by small open reading frames (sORFs) are an emerging class of functional molecules that regulate key cellular processes. Their study is hampered by several methodological challenges, including their small size, low abundance, and the difficulty in generating specific antibodies. This review systematizes current approaches for the identification and functional characterization of micropeptides. We describe the main strategies for their discovery: bioinformatic algorithms, global translation analysis via ribosome profiling, direct detection by mass spectrometry-based proteomics, and phenotypic screenings. Additionally, methods for functional validation and the elucidation of their molecular mechanisms of action are reviewed, including genetic knockouts and affinity tagging for visualization and the study of protein-protein interactions. The review discusses the key challenges and future prospects of the field, emphasizing the importance of an integrated multi-omics approach for the comprehensive mapping of the micropeptidome.
Biochemistry. 2025;90(11):1621-1637
1621-1637
NEW ASPECTS OF PROTEIN BIOSYNTHESIS INHIBITION BY PROLINE-RICH ANTIMICROBIAL PEPTIDES
Аннотация
Proline-rich antimicrobial peptides (PrAMPs) are promising compounds for overcoming antibiotic resistance, one of the global health threats, and stand out from other types of AMPs by their high safety profile. The main cellular target of PrAMPs, like most modern antibiotics, is the conservative cellular structure – the ribosome. PrAMPs bind in the ribosomal tunnel, forming multiple interactions with nucleotides of 23S rRNA, and are divided into two classes depending on their mechanism of action: inhibition of elongation or termination. The N-terminal part of the peptides, which is important for the activity of class I peptides, extends into the A-site pocket, preventing the binding of aminoacyl-tRNA. A new family of PrAMPs, runicidins, was discovered using genomic search methods. Its representatives have the longest N-terminal part, as well as a unique pair of amino acids Trp23 and Phe24 at the C-terminus. The Trp-Phe dyad forms a spacer at the constriction site of the ribosomal tunnel, stabilizing the binding and leading to increased antibacterial activity. New structural studies of the class I peptide Bac5 have demonstrated its ability to disrupt the correct positioning of the CCA end of the P-site tRNA in the peptidyltransferase center of the ribosome, which can affect the assembly of functional initiation complexes. Class II PrAMPs, according to new data, have additional binding sites on the ribosome and have a complex effect on the bacterial cell: they disrupt the termination of protein synthesis, block the cellular ribosome release system, prevent the correct assembly of the 50S ribosomal subunits, and, possibly, affect the first stage of translocation. Recent studies expand our understanding of the antimicrobial activity of PrAMPs and contribute to the creation of future therapeutic drugs based on AMPs.
Biochemistry. 2025;90(11):1638-1656
1638-1656
THE E-STORY NEVER ENDS
Аннотация
In this review article, the functional role of the E-site of the ribosome is discussed in the light of modern structural data. According to traditional concepts, this site is intended only for binding deacylated tRNA (E-tRNA) preceding the dissociation of this molecule from the protein synthesizing complex. Specific contacts of E-tRNA with rRNA of large ribosome subunits from different sources, as well as the sequence of their formation and destruction are considered. The mechanism of translation suppression by inhibitors whose binding site is the E-site of the ribosome is considered. Based on modern data on the localization of aminoacyl-tRNA synthetases (APC) in the immediate vicinity of the ribosome, a hypothesis is formulated that one of the main purposes of the E-site of the ribosome is the modulated preparation of tRNA for the formation of a specific complex with APC, in the form of which it leaves the ribosome.
Biochemistry. 2025;90(11):1657-1669
1657-1669
LONG NON-CODING RNA JPX: STRUCTURE, FUNCTIONS, AND ROLE IN CHROMATIN ARCHITECTURE
Аннотация
Long non-coding RNAs (lncRNA) are new key regulators of cellular processes and biomarkers of various pathologies. JPX is a multifunctional lncRNA that is involved in the regulation of transcription, translation, and chromatin structure. JPX influences transcription and enhancer-promoter communication by controlling the activity of DNA binding proteins, particularly the chromatin architectural protein CTCF. In addition, JPX can also interact with microRNAs and mRNA stabilizing/degrading proteins, thereby regulating translation in the pathogenesis of oncological and other diseases. The study of JPX opens up new directions in the field of molecular methods of genome regulation. This review summarizes the accumulated knowledge about the structure, evolutionary origin and functions of the lncRNA JPX.
Biochemistry. 2025;90(11):1670-1688
1670-1688
BIOMOLECULAR CONDENSATES IN REGULATION OF TRANSCRIPTION AND CHROMATIN ARCHITECTURE
Аннотация
Recent research highlights the pivotal role of liquid-like complexes – biomolecular condensates – in gene control. Biomolecular condensates involve enhancers and gene promoters into microenvironments with specific composition, capable of both activating and repressing transcription or maintaining its appropriate level. Aside from that, condensates can influence chromatin structure and are important participants in enhancer-promoter communication. Finally, condensates represent a perspective therapeutic target, as their misregulation results in a broad spectrum of pathologies. In this review, we cover most recent as well as fundamental research establishing the role for condensates in gene expression regulation and enhancer-promoter communication.
Biochemistry. 2025;90(11):1689-1707
1689-1707
20 YEARS OF DNA BARCODING – SOME RESULTS AND PROBLEMS
Аннотация
Over 20 years of very active work on DNA barcoding of various types of multicellular organisms, specific markers have been selected for many groups, primers were developed for many selected markers, DNA barcodes were obtained for more than 400 thousand species, and a special BOLD database was created. Next-generation sequencing methods allow DNA barcodes to be obtained immediately for many objects, including for various samples stored in museum collections. DNA barcode analysis reveals many previously unknown and undescribed species in various animal groups. Successes have been achieved in various areas of practical application of DNA barcodes. However, many problems and controversial issues remain, primarily in the possibility of describing new species based on DNA barcodes, as well as in the accuracy of identifying samples using reference libraries.
Biochemistry. 2025;90(11):1708-1726
1708-1726
A UNIQUE MECHANISM OF GLYCINE-SPECIFIC INHIBITION OF BACTERIAL TRANSLATION BY BOTTROMYCIN A2
Аннотация
The rise of antimicrobial resistance among pathogenic bacteria poses a critical challenge to modern medicine, highlighting an urgent need for novel therapeutic agents. Bottomycin A2 (BotA2) is a promising candidate for future drug development, demonstrating potent activity against clinically relevant pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Mycoplasma species, although its molecular mechanism of action has remained unclear until now. Here, we demonstrate that BotA2 inhibits bacterial translation with unique context specificity determined by the mRNA coding sequence. Using high-throughput toe-printing coupled with deep sequencing (Toe-seq analysis), we show that BotA2 induces ribosome pausing predominantly when a glycine codon enters the A-site of the ribosome, regardless of the codon identities in the P- and E-sites. Our biochemical and biophysical data indicate that BotA2 specifically arrests glycine-delivering ternary complexes on the ribosome, thereby preventing full accommodation of incoming Gly-tRNAGly within the peptidyl transferase center. Altogether, our findings uncover a previously undescribed mechanism of translation inhibition, driven by the context-specific immobilization of ternary complexes on elongating ribosomes.
Biochemistry. 2025;90(11):1727-1753
1727-1753
CELLULAR PROTEINS Hsp60 AND SAHH AS NEGATIVE REGULATORS OF EARLY STAGES OF HIV-1 REPLICATION
Аннотация
The increasing over-time HIV-1 resistance to drugs targeting viral proteins necessitates the search for new targets, including blockers of interactions between viral and cellular proteins. Inhibitors of binding have already been identified for two cellular proteins (LEDGF/p75 and Ku70) that interact with viral integrase, reducing replication efficiency. Previously, using cross-linking and co-immuno-precipitation followed by mass spectrometry, several new cellular potential partners of HIV-1 integrase were discovered, including the chaperonin Hsp60 and adenosylhomocystein hydrolase SAHH. In this study, we demonstrated that these purified recombinant proteins co-precipitate in vitro with integrase, indicating their ability to directly interact with it. It was found that knockdown of Hsp60 and SAHH in human cells enhances the efficiency of HIV-1-based pseudovirus transduction. Moreover, this effect occurs specifically at the early stages of HIV-1 replication rather than at the proviral transcription stage. Additionally, we were able to determine the stage of the HIV-1 replication cycle affected by these proteins. It was shown that Hsp60 knockdown stimulates integration, while SAHH knockdown increases the efficiency of viral reverse transcription, in which integrase is also involved.
Biochemistry. 2025;90(11):1754-1764
1754-1764
THE REPORTER SYSTEM FOR THE DETECTION OF G-QUADRUPLEXES IN THE PROMOTER REGION OF THE HUMAN TELOMERASE REVERSE TRANSCRIPTASE GENE
Аннотация
In 80–100% of cases, the transformation of human somatic cells into tumor cells is associated with of the catalytic subunit of telomerase, reverse transcriptase (hTERT), increased expression. hTERT gene transcription inhibition in tumor cells may become one of the approaches to antitumor therapy. The hTERT promoter contains a G-rich region with a length of 68 nucleotides, which is capable of forming G-quadruplexes (G4) under certain conditions in vitro. It is known that G4s interfere with the human RNA polymerases activity. Thus, G4 structure stabilization in the promoter can be considered as a possible way to reduce hTERT expression. To prove the G4 formation in the G-rich sequence of the hTERT promoter in a double-stranded supercoiling DNA, plasmid constructs based on the pRFPCR plasmid were obtained. The plasmids contained genes of fluorescent proteins (RFP and Cerulean) and the central hTERT promoter region G4. The hTERT promoter region central G4 formation in the obtained constructs was demonstrated with the DNA polymerase stop assay method. The influence of G228A and G250A substitutions on G4 stability in physiological conditions was investigated. It was established that the low molecular weight ligands BRACO19 and TMPyP4, well-studied stabilizers of the G4 structure, can effectively interact with the hTERT promotor central G4 in the range of concentrations 5–25 μM.
Biochemistry. 2025;90(11):1765–1780
1765–1780
SERINE PEPTIDASE HOMOLOG FROM THE BEETLE Tenebrio molitor WITH SUBSTITUTION OF SERINE RESIDUE WITH THREONINE IN THE CATALYTIC TRIAD
Аннотация
Analysis of the genomes and transcriptomes of the beetle Tenebrio molitor revealed a group of six serine peptidase homologs (SPH) of the S1A chymotrypsin subfamily containing a conservative substitution of the catalytic residue Ser195 with Thr (Ser195Thr) in the active center. All six SPH are secreted proteins with prepropeptides and lack regulatory domains in the propeptide. The most highly expressed homolog, SerPH122, shares 57% sequence identity with the most highly expressed elastase-like peptidase of T. molitor, SerP41. Both proteins exhibit similar domain organization, localization in the posterior midgut, and expression patterns in the feeding stages of the fourth instar larva and imago. Testing hydrolytic activity of the recombinant rSerPH122 preparation demonstrated that the conservative substitution of Ser for Thr in the active center did not abolish its catalytic activity. rSerPH122 exhibits low specific activity but broad substrate specificity, most effectively hydrolyzing substrates of chymotrypsin-like and trypsin-like peptidases. The homolog has a pH optimum at 8.5 and is stable in the pH range 4.0-8.0. This study addresses the question of activity of the homologs with the Ser195Thr substitution and contributes to understanding of the poorly studied area of SPH functions, providing a basis for elucidating relationship between the structure and function of serine peptidases and their homologs.
Biochemistry. 2025;90(11):1781–1793
1781–1793
RELATIONSHIPS OF GDAPI MUTATIONS TO DISEASE PHENOTYPE AND MECHANISMS OF THERAPEUTIC ACTION OF ACTIVATORS OF OXIDATIVE METABOLISM IN A PATIENT WITH CHARCOT-MARIE-TOOTH NEUROPATHY TYPE 2K
Аннотация
Development of personalized medicine, including treatments of hereditary diseases, requires translation of biochemistry advances into medical practice. Our work is dedicated to solving this problem in a clinical case of hereditary Charcot-Marie-Tooth neuropathy 2K (CMT2K) due to compound-heterozygous mutations in GDAPI gene, leading to the protein variants with the most common in Europe substitution L239F (from the father) or with a previously uncharacterized substitution A175P (from the mother). The ganglioside-induced, differentiation-associated protein GDAPI encoded by the GDAPI gene, is localized to the outer mitochondrial membrane and belongs to the glutathione-S-transferase superfamily. Our structure-function analysis of GDAPI shows that dimerization of the monomers with either L239F or A175P substitutions, along with the half-of-the-sites reactivity of GDAPI to hydrophobic ligands, may synergistically impair the binding. This mechanism explains the early onset and progress of the disease in a child, whereas the heterozygous parents are asymptomatic. Published phenotypes of the amino acid substitutions in the GDAPI region comprising the binding site for hydrophobic compounds, including the phenotypes of the homozygous L239F substitution and its compound-heterozygous combinations with other substitutions in this region are analyzed. Association of the regional substitutions with axonal form of CMT and disturbances in the thiamine diphosphate (ThDP)- and NAD+-dependent mitochondrial metabolism is revealed. Hence, the therapeutic effect of the precursors of these coenzymes, thiamine and nicotinamide riboside (NR), is studied. Oral administration of the precursors to the patient leads to increased levels of ThDP and NAD+ in the whole blood, an improvement in the hand grip strength, and, after the long-term administration, to normalization of ThDP-dependent metabolism. That is, after the therapy, the disease-altered levels of the translketolase (TKT) activity and its apoform, as well as the relationships between the levels of the holoenzyme TKT, ThDP and NAD+ in the patient's blood, approach those of healthy women. Our results demonstrate the therapeutic potential of thiamine and NR in correcting metabolic dysregulation in CMT caused by GDAPI mutations, suggesting the underlying molecular mechanisms. Genetic diagnostics and biochemical characterization of the mechanisms of mutation pathogenicity may increase efficiency of the therapy in clinically asymptomatic or early stages of the disease, as it is easier to protect from the accumulating metabolic damage than to reverse the damage.
Biochemistry. 2025;90(11):1794–1815
1794–1815
COMPARATIVE ANALYSIS OF THE RNA-CHROMATIN INTERACTOME DATA: RESOLUTION, COMPLETENESS, AND SPECIFICITY OF DATA
Аннотация
Two types of experiments are used to study RNA-chromatin interactions: a search for the interactome of individual RNAs (“one-to-all” or OTA) and a genome-wide search for contacts of all RNAs (“all-to-all” or ATA). A comparative analysis of ATA and OTA data revealed their fundamental differences in resolution, completeness, and specificity. OTA data provide high resolution (~1000 bp) and reproducibility (~90%), serving as a “gold standard”. In contrast, ATA data have lower resolution (~5000 bp), and their reproducibility (<10%) is critically dependent on the protocol, with the two-step fixation using disuccinimidyl glutarate and formaldehyde (GRID-seq) showing a clear advantage over formaldehyde alone. The introduced “chromatin potential” metric and filtering for BaRDIC peaks effectively isolate the specific signal. This work proposes a strategy for reliable interactome analysis: combining the selection of RNAs based on chromatin potential with the use of concordant contacts from peaks.
Biochemistry. 2025;90(11):1816-1829
1816-1829
CONFLICTING PHYLOGENETIC SIGNAL BETWEEN NUCLEAR RIBOSOMAL DNA AND PLASTOME DATA AS EVIDENCE FOR HYBRID ORIGIN OF A TETRAPLOID MEMBER OF Salicornia (Amaranthaceae s.l.)
Аннотация
Species of the genus Salicornia (Amaranthaceae s.l.) are widespread throughout the globe and are resistant to salinity. They can be used as food and for biofuel production. The formation of pure lines as a result of self-pollination along with the possibility of sporadic cross-pollination, polyploidy, a high degree of physiological plasticity and a small number of diagnostic characters greatly complicate the taxonomy of the genus. Salicornia is an evolutionarily young group, where the number of informative substitutions in traditionally analyzed regions of nuclear and plastid DNA turned out to be insufficient to establish relationships between species, and the very concept of a species in this genus remains a subject of debate. To clarify the relationships of the Eastern European species, we used high-throughput sequencing to determine the sequences and perform a phylogenetic analysis of the plastomes of 11 samples representing all the main morphotypes of the Eastern European glassworts, and analyzed the variability of the nuclear rDNA external transcribed spacer (nrETS). The sizes of the assembled plastomes varied from 153,290 bp to 153,504 bp and had a typical architecture with a large single-copy region (84,625-84,797 bp in length), a small single-copy region (18,818-18,870 bp in length), and two inverted repeats (24,898-24,908 bp in length). Comparison of phylogenetic trees reconstructed from all currently available plastome data and nrETS alignments of the same glasswort accessions revealed a discrepancy in the arrangement of tetraploid S. procumbens subsp. pojarkovae and S. brachiata accessions, which show affinities to different lineages depending on the use of plastid or nuclear (nrETS) data. Our results highlight the role of reticulate evolution in the genus Salicornia.
Biochemistry. 2025;90(11):1830–1842
1830–1842
GENE ORDER IN MITOCHONDRIAL DNA AFFECTS THE ABUNDANCE OF THEIR TRANSCRIPTS (A CASE OF MARINE NEMATODES)
Аннотация
Mitochondrial genomes of most animals contain the same set of genes, with all or many protein-coding genes (PCGs) arranged in the same order, forming conserved blocks termed syntenies. Some syntenies have been preserved for hundreds of millions of years and are found in both vertebrates and invertebrates. This evolutionary conservation indicates a functional role for PCG arrangement; however, the biochemical and/or physiological mechanisms by which gene order in mtDNA affects viability are unknown. Among animals, there are taxa that have completely lost conserved syntenies in mtDNA. Canonical animal syntenies in mtDNA had not been reported in nematodes, until some were recently discovered in previously unstudied nematode taxa, including the marine family Thoracostomopsidae (Nematoda, Enoplida). We sequenced the complete mitochondrial genomes of three thoracostomopsid species, determined the gene order and their expression levels from RNA-seq data integrated for the family representatives in all available databases. It was found that six species of the Thoracostomopsidae reveal three distinct patterns of PCG arrangement, where relative mRNA levels correlate with gene order rather than species phylogeny. We hypothesize that the influence of PCG translocations on their expression levels underlies the long-term preservation of mitochondrial syntenies among animals.
Biochemistry. 2025;90(11):1843-1861
1843-1861
METTL4 METHYLTRANSFERASE ACTIVITY IS ESSENTIAL FOR MAINTAINING OPTIMAL SPLICING EFFICIENCY IN HeLa S3 CELLS
Аннотация
Methyltransferases that modify spliceosomal small nuclear RNAs (snRNAs) play an important role in the cell, ensuring the correct maturation of snRNAs, which, in turn, is necessary for the optimal functioning of the spliceosome. In this work, we studied the enzyme METTL4, which performs N6-methylation of 2′-O-methyladenosine at position 30 of U2 snRNA. The function of both the protein and the modification in splicing is currently unclear. We showed that inactivation of METTL4 gene in HeLa S3 cells results in significant change in alternative splicing, a general slowing of splicing and accumulation of introns. In cells without METTL4, the expression of genes associated with the maturation of ribosomal RNA is decreased, and in the nuclei of these cells the number of coilin-positive structures, most likely Cajal bodies, is reduced.
Biochemistry. 2025;90(11):1862-1878
1862-1878
Discussion
CYSTEINE CATHEPSINS AND DRUG DISCOVERY: WHAT WE KNOW AND WHAT WE SHOULD KNOW
Аннотация
Cysteine cathepsins are a group of closely related proteolytic enzymes active at low pH. The most well-studied function of these enzymes is protein degradation within lysosomes. However, accumulating evidence suggests that cysteine cathepsins also function at physiological pH levels in other cellular compartments outside lysosomes, as well as in the extracellular space. Many of these extra-lysosomal functions of cysteine cathepsins are typically associated with pathological processes, contributing to conditions such as oncogenesis and metastasis, neurodegenerative diseases, cardiovascular disorders, and autoimmune and inflammatory processes. Consequently, cysteine cathepsins have been proposed as diagnostic and prognostic molecular markers, as well as pharmacological targets. Notably, the pathological processes involving these enzymes often operate independently of their classical lysosomal functions. This work aims to outline key questions, the answers to which could enhance our understanding of the fundamental mechanisms governing the extra-lysosomal functions of cysteine cathepsins. Addressing these questions is also critical for developing novel therapeutic strategies to treat diseases in which cysteine cathepsins play a pathogenic role.
Biochemistry. 2025;90(11):1879-1886
1879-1886
IN SEARCH OF NOVEL DIAGNOSTIC BIOMARKERS FOR PSYCHONEUROLOGICAL AND NEURODEGENERATIVE DISEASES: TRANSLATION FACTORS DENR AND eIF2D
Аннотация
A rising global prevalence of psychoneurological and neurodegenerative disorders emphasizes the critical need for effective therapeutics and methods for early and highly sensitive diagnostics in order to ensure efficient and timely treatment of these disorders. Expanding the range of available biomarkers for better characterization of disease features and progression is a promising direction in modern diagnostics. The discovery of novel biomarkers depends on elucidating molecular mechanisms underlying disease development and pathogenesis. Numerous psychoneurological and neurodegenerative disorders are associated with the dysregulation of protein translation. The review summarizes information on the action mechanisms of translation factors DENR and eIF2D and evaluates their potential as diagnostic biomarkers for psychoneurological and neurodegenerative diseases.
Biochemistry. 2025;90(11):1887-1896
1887-1896