SEARCH · PubMed Health

Results for “Processing Bodies”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Phosphoproteomics identifies the DYRK1B protein kinase as a regulator of processing bodies.

Dual-specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) modulates the cell cycle and cell fate during development, and is deregulated in cancer and metabolic syndrome. However, only a few DYRK1B substrates have been defined, so we undertook a phosphoproteomics screen in cells that exhibit inducible DYRK1B expression. Motif analysis revealed enrichment for proline-directed serine or threonine phosphorylation sites (pSer-Pro or pThr-Pro), consistent with the consensus motif of class I DYRKs. Gene Ontology (GO) analysis revealed enrichment of proteins involved in mRNA binding, mRNA processing and ribonucleoprotein complexes. Several processing body (PB) components, including DCP1A, PATL1 (PAT1B), EDC3 and 4E-T (also known as EIF4ENIF1), were identified as DYRK1B-inducible phosphoproteins. DYRK1B also co-immunoprecipitated with DCP1A, PAT1B, EDC3, EDC4, DDX6 and XRN1. Super-resolution microscopy demonstrated that DYRK1B co-localised with DCP1A, DCP1B and DDX6 in PBs. Expression of DYRK1B increased PB abundance, whereas inhibition, depletion or knockout of DYRK1B reduced phosphorylation of DCP1A and 4E-T and decreased PB number. Re-expression of wild-type but not kinase-dead DYRK1B restored PB numbers in knockout cells. These findings reveal novel DYRK1B targets and establish DYRK1B as a regulator of PB abundance.

Dyrk Kinases↗

PubMed2026

Targeting the Microbiota-Gut-Brain Axis: Emerging Nanomedicine Approaches for Neurodegenerative Diseases.

The microbiota-gut-brain axis (MGBA) is a bidirectional relationship between the gut microbiota (GM) and the brain, where the GM affects the gastrointestinal tract (GIT) and the central nervous system (CNS), and vice versa. Microbiotas are important for several vital body processes, including metabolism, immunity, and homeostasis. The MGBA has three main pathways: the vagal nerve mechanism, the immune-related mechanism, and the neuroendocrine mechanism. GM imbalance, known as dysbiosis, affects the GIT, the brain, and the CNS. Furthermore, dysbiosis is linked to several neurological disorders such as Alzheimer's (AD), Parkinson's (PD), depression, autism spectrum disorder (ASD), and multiple sclerosis (MS). Studying MGBA gives researchers new therapeutic ideas using microbiota. Using special diets rich in fiber and probiotics, in addition to fecal microbiota transplantation (FMT), is being studied as a new therapy for MGBA. From the point of view that these therapeutic interventions maintain microbiota imbalance, which in turn will affect the brain and can relieve the neurological disorders caused by dysbiosis and MGBA.

Humans↗

PubMed2025

Detecting known neoepitopes, gene fusions, transposable elements, and circular RNAs in cell-free RNA.

MOTIVATION: Cancer is the second leading cause of death worldwide, and although there have been advances in treatments, including immunotherapies, these often require biopsies which can be costly and invasive to obtain. Due to lack of pre-emptive cancer detection methods, many cases of cancer are detected at a late stage when the definitive symptoms appear. Plasma samples are relatively easy to obtain, and they can be used to monitor the molecular signatures of ongoing processes in the body. Profiling cell-free DNA is a popular method for monitoring cancer, but only a few studies have explored the use of cell-free RNA (cfRNA), which shows the recent footprint of systemic transcription. RESULTS: Here, we developed FastNeo, a computational method for detecting known neoepitopes in human cfRNA. We show that neoepitopes and other biomarkers detected in cfRNA can discern Hepatocellular carcinoma patients from the healthy patients with a sensitivity of 0.84 and a specificity of 0.79. For colorectal cancer we achieve a sensitivity of 0.87 and a specificity of 0.8. An important advantage of our cfRNA based approach is that it also reports putative neoepitopes which are important for therapeutic purposes. AVAILABILITY AND IMPLEMENTATION: The FastNeo package is available at https://github.com/yashumayank/FastNeo and https://zenodo.org/records/11521368. The benchmark pipelines to detect Immune Epitope database and Tumor-Specific Neoantigen database neoepitopes using HaplotypeCaller, bcftools, and Lofreq, and to run FastNeo with STAR instead of Bowtie2 are also available in the above github repository.

Humans↗

PubMed2026

Motor coordination and behavioural deficits in a mouse model of KMT2B-related dystonia.

INTRODUCTION: Pathogenic variants in KMT2B cause early-onset dystonia, but a mouse model that has undergone comprehensive, dystonia-oriented phenotyping is lacking. METHODS: We conducted detailed phenotyping on heterozygous Kmt2b constitutive knockout mice and wild-type littermates, assessing growth, neurobehavioural traits, motor coordination, sensorimotor gating, social behaviour and metabolic parameters, combined with striatal RNA sequencing. RESULTS: Kmt2b knockout mice of both sexes were viable but significantly smaller and lighter than littermate controls. Knockouts were hyperlocomotive in the open field and showed approximately two-fold larger acoustic startle responses; unexpectedly, prepulse inhibition was enhanced rather than reduced at all prepulse intensities. On the balance beam, knockouts crossed more slowly and paused more frequently; female knockouts also paused more on the ladder rung task. Frame-by-frame video analysis revealed a claw-like hindpaw posture characterized by abnormal inward flexion of the digits. Knockout mice spent less time investigating a novel conspecific, while social recognition memory remained intact. Striatal RNA sequencing confirmed reduction of Kmt2b transcript to approximately half of control levels and identified 177 differentially expressed genes, including Maob, encoding monoamine oxidase B; gene set enrichment analysis implicated neurodevelopmental, glial and mitochondrial processes. Nociception, vision, body-weight-adjusted grip strength, and clinical chemistry and haematological measures were largely unaffected. CONCLUSION: Heterozygous Kmt2b knockout mice show hyperlocomotion, altered sensorimotor gating, impaired motor coordination with dystonic-like paw posturing and reduced sociability, alongside a striatal transcriptomic signature implicating neurodevelopmental processes. The model mirrors aspects of human KMT2B-related dystonia and provides a platform for mechanistic study; environmental or pharmacological challenge may be needed to unmask overt dystonic features.

Dystonia↗

PubMed2026

Male and Female Mice Show Similar Fear Memory Performance Despite Hippocampal Immediate Early Gene Expression Differences During Encoding and Consolidation.

Accurate and efficient memory processing is essential for survival. A body of ongoing work in both human subjects and animal models suggests that memory processing may differ substantially between males and females. In mice, contextual fear memory (CFM) encoding, consolidation, and recall have been well studied, and the mouse hippocampus and amygdala have been implicated in these processes. The present pilot study addresses whether the activation of these brain regions differs substantially between male and female mice at each stage of CFM processing. We find that male and female mice show no differences in sleep behavior, which is essential for CFM consolidation, following single-trial contextual fear conditioning (CFC). We also find no significant differences in CFM recall performance between male and female mice. However, females show a trend for larger increases in CA1 cFos expression, relative to males, during CFM encoding. On the other hand, only males-but not females-show an apparent increase in cFos expression among dentate gyrus (DG) granule cells during CFM consolidation. Males also show a trend for a larger apparent reduction in cFos in CA1 and CA3 during CFM consolidation, relative to females. These preliminary findings highlight the idea that the neurobiological underpinnings of memory processing may differ between males and females, even when performance during recall is identical.

Animals↗

PubMed2026

How, When, and for Whom Does Daily Weight Bias Internalization Undermine Body Image Satisfaction? A Daily Diary Study of Perceived Weight, Exercise Duration, and Gender Differences Among Adolescents.

Although body image satisfaction is increasingly recognized as a dynamic experience that fluctuates across daily contexts, little is known about how weight bias internalization shapes these fluctuations or the cognitive mechanisms and contextual factors involved. The present study examined whether perceived weight mediates the association between weight bias internalization and body image satisfaction, whether exercise duration moderates this association, and whether these effects differ by gender. Daily diary data were collected over 10 consecutive days from 305 Chinese adolescents (Mage = 12.59 years, SD = 0.63 years; 49.2% girls). Multilevel analyses revealed that, at both within- and between-person levels, higher weight bias internalization was associated with lower body image satisfaction. Perceived weight significantly mediated the association between weight bias internalization and body image satisfaction at both levels. Additionally, exploratory analyses using dynamic structural equation modeling further indicated that perceived weight mediated the relationship between weight bias internalization and body image satisfaction at the between-person level, but not at the within-person level. Furthermore, exercise duration moderated the association between perceived weight and body image satisfaction among female adolescents but not among male adolescents. Specifically, the negative association between perceived weight and body image satisfaction was stronger on days when girls engaged in more exercise than usual and among girls with higher average exercise duration. In addition, exercise duration moderated the indirect association between weight bias internalization and body image satisfaction through perceived weight at both within- and between-person levels among girls. These findings highlight the dynamic cognitive processes linking weight bias internalization to body image satisfaction, and the importance of considering gender and daily exercise context in understanding adolescents' body image experiences.

Humans↗

PubMed2026

Ultra-processed Foods, Cancer, and Early-onset Cancer: A Comprehensive Review.

The classification of foods according to their degree of processing, and particularly the concept of ultra-processed foods, is relatively new. Consumption of ultra-processed foods has increased markedly worldwide in recent decades. Their growing consumption has coincided with a rising global burden of cancer, including marked increases in several cancers diagnosed before age 50 years. In this comprehensive review, we summarize trends in ultra-processed food consumption and the sociodemographic, psychological, and behavioral characteristics associated with higher intake. We further review the epidemiological evidence linking ultra-processed foods with cancer incidence and mortality, with particular attention to the limited but emerging evidence relevant to early-onset cancer. Potential mechanisms linking ultra-processed foods to cancer include unfavorable nutrient displacement, changes in body composition and fat deposition, and increased exposure to additives, processing by-products, and other chemicals. These influences may converge on a range of biological pathways, including metabolic dysfunction, chronic inflammation, immune dysregulation, gut microbiome disruption, DNA damage and genomic instability, and epigenetic alterations. Substantial uncertainties remain, including heterogeneous exposure definitions and classification practices, limitations in dietary assessment and temporal exposure capture, residual confounding, and the complexity of putative biological mechanisms. We conclude by highlighting key research challenges and future directions, along with considerations related to policy, regulation, and industry practices.

Ultra-processed foods↗

PubMed2025

Trade-off between antibacterial immune defense and oogenesis progression in female Drosophila melanogaster.

Trade-offs between reproduction and immunity are common in animals, potentially due to preferential allocation of limiting resources. In Drosophila melanogaster, mating stimulates egg production but also triggers a rapid and persistent decrease in female immune defense. Proteins essential for both processes are produced in fat body tissue, which may result in competition for cellular resources that could drive a functional trade-off between reproduction and immune defense. We predicted that arrest of oogenesis prior to egg provisioning would alleviate postmating immune suppression because cellular stress would be relieved, but that postmating immune suppression would be observed in genotypes that fully provision eggs even if fertility is compromised. In the present study, we test these predictions by evaluating postmating immune competence in mated D. melanogaster mutants that arrest oogenesis either prior to, or subsequent to, vitellogenesis. Consistent with our prediction, we find that mated female immune defense is maintained when egg development is arrested prior to vitellogenesis. We find that progression through the vitellogenic stages of oogenesis results in postmating immune suppression, except in the case of a mutant with an egg-retention phenotype, where we infer that the failure to lay eggs results in feedback that inhibits subsequent egg development. We additionally show that elimination of yolk protein synthesis in the fat body and follicle cells of the ovary partially restores female immune capacity. Nevertheless, females that lack yolk protein genes still experience partially reduced immune capacity after mating, suggesting that other reproductive demands also suppress immune defense.

Animals↗

PubMed2025

Breaking anterior-posterior symmetry in the moth fly Clogmia albipunctata.

Establishing the anterior-posterior (AP) body axis is a fundamental process during embryogenesis, and the fruit fly, Drosophila melanogaster, provides one of the best-known case studies. But for unknown reasons, different species of flies (Diptera) establish the AP axis through unrelated, structurally distinct anterior determinants (ADs). The AD of Drosophila, Bicoid (Bcd), initiates symmetry-breaking during nuclear cleavage cycles (NCs) when ubiquitous pioneer factors, such as Zelda (Zld), drive zygotic genome activation (ZGA) at the level chromatin accessibility by nucleosome depletion. While Bcd engages in a concentration-dependent competition with nucleosomes at the loci of a small set of transcription factor (TF) genes that are expressed in the anterior embryo, it remains unknown whether unrelated ADs of other fly species function in the same way and target homologous genes. We have examined the symmetry-breaking mechanism of a moth fly, Clogmia albipunctata, in which a maternally expressed transcript isoform of the pair-rule segmentation gene odd-paired serves as AD. We provide a de novo assembly and annotation of the Clogmia genome and describe how Clogmia's orthologs of zelda (Cal-zld) and odd-paired (Cal-opa) affect chromatin accessibility and gene expression. Our results suggest direct roles of Cal-zld in opening and closing chromatin during nuclear cleavage cycles (NCs) and show that during the early phase of ZGA maternal Cal-opa activity promotes chromatin accessibility and anterior expression at Clogmia's homeobrain and sloppy-paired loci. These genes are not known as key targets of Bcd but may serve a more widely conserved role in the initiation of anterior pattern formation given their early anterior expression and function in head development in insects. We conclude that the ADs of Drosophila and Clogmia differ in their target genes but share the mechanism of concentration-dependent nucleosome depletion.

Journal Article↗

PubMed2026

Prior exposure to hypoxia alters DNA methylation patterns in the eastern oyster.

Environmentally induced epigenetic changes (e.g., DNA methylation) can alter genetic activity to help organisms adapt and respond to variable environments. While many studies have investigated DNA methylation as a response to a stressor at a single timepoint, less well-understood is how methylation may encode memory of past environments and influence the response to current environments (i.e., carryover effects). Oysters are an excellent natural system to study carryover effects due to their sessile nature, which may expose them to increased environmental variability. To better understand how methylation changes in response to a previous exposure of environmental stress, we conducted a fully factorial experiment exposing juvenile oysters to either control or hypoxic conditions at two timepoints separated by 60 days. After the second exposure, whole body tissue samples were collected and processed for methylRAD sequencing. Regardless of treatment, methylation was mostly found in exons. We found both the first and second exposure treatments contributed significantly to the observed variation in gene body methylation. Interestingly, oysters that were first exposed to hypoxia and later exposed to control conditions had methylation patterns that differed the most from any other condition. We found that differentially methylated genes identified in pairwise comparisons were mainly involved in the oxidative stress response, metabolism, and transcription. Together, these findings suggest that early life environments have a lasting impact on the epigenome and that the timing of stress elicits unique response strategies, which highlights potential targets of resilience for oysters.

Animals↗

PubMed2026

Immunoinformatics Approach for Optimization of Targeted Vaccine Design: New Paradigm in Clinical Trials and Healthcare Management.

INTRODUCTION: The immunoinformatics approach combines bioinformatics and computational tools, offering a revolutionary method for improving vaccine development by analyzing immune responses at the molecular level. Immunoinformatics enables the creation of customized vaccines designed for specific infections or cancer cells. OBJECTIVE: The primary objective of immunoinformatics is to enhance the vaccine development process by predicting and boosting the body's immune response. It aims to identify potential immunogenic epitopes and biomarkers that are important for creating vaccines with greater specificity and efficacy, especially when dealing with large-scale data. METHODS: Immunoinformatics utilizes a combination of proteomic, genomic, and epigenomic data, as well as machine learning algorithms and artificial intelligence techniques. These tools predict how various immunological components, e.g., T-cell and B-cell epitopes, interact with the immune system. This approach allows researchers to avoid traditional trial-and-error methods, enabling the efficient identification of potential vaccine candidates. Additionally, personalized vaccines can be developed by considering individual genetic and immunological characteristics. RESULTS: The use of immunoinformatics techniques accelerates the screening of vaccine candidates, enhances patient stratification, and optimizes formulations for clinical trials. This approach has been shown to improve vaccine safety, efficacy, and development speed. It also holds promise for managing healthcare on a large scale by producing vaccines tailored to specific populations, thereby improving the overall effectiveness of vaccination programs. CONCLUSION: Immunoinformatics represents a transformative approach to vaccine research, improving clinical trial efficiency and enabling the development of more reliable, flexible, and personalized vaccines. This approach has the potential to significantly enhance global healthcare outcomes by accelerating the vaccine development process and optimizing vaccination strategies.

Immunoinformatics↗

PubMed2023

The gastropod Lottia peitaihoensis as a model to study the body patterning of trochophore larvae.

The body patterning of trochophore larvae is important for understanding spiralian evolution and the origin of the bilateral body plan. However, considerable variations are observed among spiralian lineages, which have adopted varied strategies to develop trochophore larvae or even omit a trochophore stage. Some spiralians, such as patellogastropod mollusks, are suggested to exhibit ancestral traits by producing equal-cleaving fertilized eggs and possessing "typical" trochophore larvae. In recent years, we developed a potential model system using the patellogastropod Lottia peitaihoensis (= Lottia goshimai). Here, we introduce how the species were selected and establish sources and techniques, including gene knockdown, ectopic gene expression, and genome editing. Investigations on this species reveal essential aspects of trochophore body patterning, including organizer signaling, molecular and cellular processes connecting the various developmental functions of the organizer, the specification and behaviors of the endomesoderm and ectomesoderm, and the characteristic dorsoventral decoupling of Hox expression. These findings enrich the knowledge of trochophore body patterning and have important implications regarding the evolution of spiralians as well as bilateral body plans.

Animals↗

PubMed2025

Steroid hormones in pain: Mechanistic underpinnings and therapeutic perspectives.

Pain is a complex sensory and emotional experience that severely affects an individual's quality of life and health status. Steroid hormones, as important regulatory substances in the human body, are extensively involved in various physiological and pathological processes. In recent years, remarkable progress has been made in the research of steroid hormones in the field of pain. They play a crucial role in the occurrence, development, and treatment of pain. This review comprehensively elaborates on the roles and therapeutic mechanisms of steroid hormones in pain, explores the performances of glucocorticoids, mineralocorticoids, sex hormones, etc. in different pain models, as well as the molecular mechanisms by which they regulate pain through genomic and non-genomic effects, aiming to provide a theoretical basis for the clinical treatment of pain.

Humans↗

PubMed2026

Refining the Genetic Contribution to Type 2 Diabetes Subtypes.

BACKGROUND: Type 2 diabetes (T2D) is a complex and highly heterogeneous disease driven in part by genetic predisposition and can be stratified into clinical subgroups to aid disease management. We recently grouped T2D subjects in the Qatar Biobank (QBB) cohort into Severe Insulin-Deficient Diabetes (SIDD), Severe Insulin-Resistant Diabetes (SIRD), Mild Obesity-Related Diabetes (MOD) and Mild Age-Related Diabetes (MARD) subtypes. Herein, we focused on the genetic makeup of these subtypes. METHODS: We used the QBB cohort (n = 13,808), of whom 2687 were with T2D, and comprehensively assessed polygenic risk scores (PGS) across T2D subtypes, investigated genetic loci associated with each subtype by leveraging the most recent and largest GWAS for T2D, evaluated SNP associations across T2D genetic clusters, and identified protein interaction pathways associated with these distinct T2D subtypes. RESULTS: MOD showed consistently lower PGS compared with other T2D subtypes across all tested scores. SIDD showed more associations with SNPs mapping to residual glycemic cluster compared with other T2D subtypes. The incremental analysis of PGS004838 demonstrated a high ΔAUC of 0.101 for SIDD and a moderate ΔAUC of 0.068 for SIRD, but not for MOD and MARD. Protein interaction analyses identified candidate subtype-associated gene networks linked to pathways related to glucose homeostasis in SIDD, insulin signalling and hepatic metabolism in SIRD, body fat distribution in MOD and vascular-related processes in MARD. CONCLUSION: We found heterogeneous genetic architectures across clinically defined T2D subtypes in a Middle Eastern population. Our findings provide evidence supporting differential polygenic burden, subtype genetic associations and subtype-associated biological pathways across T2D subtypes. These observations support the utility of subtype-based genetic analyses for improving biological understanding of T2D heterogeneity.

Humans↗

PubMed2026

Genetic overlap between depression and C-reactive protein levels: Evidence from a cross-trait analysis.

Inflammation and depression have been consistently associated, with elevated C-reactive protein (CRP) levels observed in a significant subset of affected individuals. However, the genetic mechanisms underlying this association remain poorly understood. We integrated results from large-scale genome-wide association studies (GWAS) of depression and CRP levels in a cross-trait analysis specifically focusing on identifying horizontally pleiotropic loci. Identified variants were stratified as concordant versus discordant based on their direction of effects on the two traits and followed up using functional annotation, gene set enrichment, and colocalization analyses. We also explored causal relationships using Mendelian Randomization (MR) analysis with extensive sensitivity analyses, including adjustment for body mass index (BMI). We identified 9 novel loci. Functional analyses revealed that concordant loci were enriched in genes linked to immune and inflammatory processes, while discordant loci mostly mapped to metabolic pathways, including lipid regulation. MR provided strong evidence for body mass index driving a causal relationship between the genetic liability of depression on CRP levels. Our findings suggest that the association between depression and CRP levels is partly driven by shared genetic influences, pointing to different biological pathways depending on whether genetic effects are concordant or discordant. These results underscore the importance of considering effect direction when assessing the genetic overlap between depression and inflammatory processes. In addition, they highlight BMI as a key factor in the causal relationship between depression and systemic inflammation.

C-Reactive Protein↗

PubMed2024

A mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight.

Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin (POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis-acting transcriptional enhancers known as nPE1 and nPE2. Because mutant mice lacking these two enhancers still showed hypothalamic Pomc mRNA, we searched for additional elements contributing to arcuate Pomc expression. By combining molecular evolution with reporter gene expression in transgenic zebrafish and mice, here, we identified a mammalian arcuate-specific Pomc enhancer that we named nPE3, carrying several binding sites also present in nPE1 and nPE2 for transcription factors known to activate neuronal Pomc expression, such as ISL1, NKX2.1, and ERα. We found that nPE3 originated in the lineage leading to placental mammals and remained under purifying selection in all mammalian orders, although it was lost in Simiiformes (monkeys, apes, and humans) following a unique segmental deletion event. Interestingly, ablation of nPE3 from the mouse genome led to a drastic reduction (>70%) in hypothalamic Pomc mRNA during development and only moderate (<33%) in adult mice. Comparison between double (nPE1 and nPE2) and triple (nPE1, nPE2, and nPE3) enhancer mutants revealed the relative contribution of nPE3 to hypothalamic Pomc expression and its importance in the control of food intake and adiposity in male and female mice. Altogether, these results demonstrate that nPE3 integrates a tripartite cluster of partially redundant enhancers that originated upon a triple convergent evolutionary process in mammals and that is critical for hypothalamic Pomc expression and body weight homeostasis.

Animals↗

PubMed2026

Mapping the causal chain from genetic risk variants to lipid dysmetabolism in Parkinson's disease.

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analysed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain to reveal pertinent mechanisms. We show that common PD risk variants at the serine palmitoyltransferase small subunit B (SPTSSB) locus, a key regulator of de novo sphingolipid biosynthesis, are associated with increased SPTSSB brain expression and elevated plasma ceramides. Additional analyses strongly support our hypothesis that a common SPTSSB causal variant is responsible for PD risk as well as the expression and metabolic quantitative trait loci. Multiple sphingolipids and fatty acid derivatives were perturbed in PD, and we identified both unique and shared features with the Alzheimer's disease metabolome. A PD acylcarnitine signature was further replicated in human post-mortem brain tissue, when comparing those with or without preclinical Lewy body pathology. Integrated analysis of complementary brain proteomic profiles revealed dysregulation of mitochondrial processes dependent on acylcarnitines, including fatty acid beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation. Our results identify promising biomarkers and reveal a causal chain linking genetic variation to altered gene/protein expression, lipid dysmetabolism, and the manifestation of PD.

Humans↗

PubMed2026

Conditional eIF2A Deletion Suggests Extra-Adipose Mechanisms Underlying Metabolic Syndrome in Total-Body eIF2A Knockout Mice.

Dynamic regulation of protein synthesis is essential for metabolic homeostasis, with translation initiation playing a key role in this process. Emerging evidence strongly indicates that in addition to canonical eukaryotic initiation factors (e.g., eIF2, eIF4E) non-canonical factors, such as eukaryotic initiation factor 2A can modulate metabolic homeostasis. eIF2A is a highly conserved eukaryotic protein originally proposed to function analogously to bacterial IF2, promoting initiator Met-tRNAi recruitment to the 40S ribosomal subunit, though its precise mechanism remains debated. To investigate its organismal role, we have previously generated the total-body eIF2A knockout mouse, which revealed eIF2A functions in lipid homeostasis, glucose tolerance, insulin sensitivity, and susceptibility to metabolic syndrome. To further determine whether adipose tissue drives these phenotypes, we presently generated adipose-specific eIF2A knockout mice. Despite dysregulation of some key adipokines, including for example, adiponectin, these mice did not develop metabolic syndrome, even under high-fat diet conditions, indicating that adipose tissue specific deficiency of eIF2A is insufficient to reproduce the metabolic defects observed in total-body knockout. However, we found that eIF2A deficiency in the liver of the total body eIF2A-KO mice can independently drive metabolic syndrome components via translational control of Lpin1 (a phosphatidate phosphatase and a transcriptional coactivator) that controls hepatic lipid storage and metabolism. eIF2A deficiency in the liver leads to disruption of fatty acid oxidation and the production of ketone bodies, not observed in adipose-specific eIF2A knockout mice. Our findings suggest that systemic metabolic effects observed in the total body eIF2A-KO mice may arise from coordinated functions across multiple organs.

adipose tissue↗