Integrative multi-omics and systems bioinformatics in translational neuroscience: A data mining perspective

Journal of Pharmaceutical Analysis, Год журнала: 2023, Номер 13(8), С. 836 - 850

Опубликована: Июль 1, 2023

Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth information, with its application to neuroscience termed neuroinformatics. Data mining enabled the generation new hypotheses based on differentially regulated biological molecules associated disease mechanisms, which can be tested experimentally for improved diagnostic therapeutic targeting neurodegenerative diseases. Importantly, integrating multi-omics data using systems bioinformatics approach will advance understanding layered interactive network regulation that exchanges systemic knowledge facilitate development comprehensive human brain profile. In this review, we first summarize studies utilizing from individual type analysis, including epigenetics/epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, spatial omics, pertaining Alzheimer's disease, Parkinson's multiple sclerosis. We then discuss integration approaches, independent unsupervised methods, more intuitive informative interpretation obtained across different layers. further assess integrate provide convoluted insights offer proof-of-concept proposition towards reconstruction networks. Finally, recommend combination high dimensional experimental validation achieve translational applications biomarker discovery, development, elucidation mechanisms. conclude future perspectives opportunities applying integrative precision phenotyping diseases personalized medicine.

Язык: Английский

---

Lost in traffic: consequences of altered palmitoylation in neurodegeneration

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Май 30, 2023

One of the first molecular events in neurodegenerative diseases, regardless etiology, is protein mislocalization. Protein mislocalization neurons often linked to proteostasis deficiencies leading build-up misfolded proteins and/or organelles that contributes cellular toxicity and cell death. By understanding how mislocalize neurons, we can develop novel therapeutics target earliest stages neurodegeneration. A critical mechanism regulating localization protein-lipid modification S-acylation, reversible addition fatty acids cysteine residues. S-acylation more commonly referred as S-palmitoylation or simply palmitoylation, which 16-carbon acid palmitate proteins. Like phosphorylation, palmitoylation highly dynamic tightly regulated by writers (i.e., palmitoyl acyltransferases) erasers depalmitoylating enzymes). The hydrophobic anchors membranes; thus, reversibility allows be re-directed from membranes based on local signaling factors. This particularly important nervous system, where axons (output projections) meters long. Any disturbance trafficking have dire consequences. Indeed, many involved diseases are palmitoylated, been identified palmitoyl-proteomic studies. It follows acyl transferase enzymes also implicated numerous diseases. In addition, work concert with mechanisms, like autophagy, affect health modifications, such acetylation, nitrosylation, ubiquitination, function turnover. Limited studies further revealed a sexually dimorphic pattern palmitoylation. Therefore, wide-reaching consequences

Язык: Английский

---

Heavy Metal Mediated Progressive Degeneration and Its Noxious Effects on Brain Microenvironment

Biological Trace Element Research, Год журнала: 2023, Номер 202(4), С. 1411 - 1427

Опубликована: Июль 18, 2023

Язык: Английский

---

Systematic identification of structure-specific protein–protein interactions

Molecular Systems Biology, Год журнала: 2024, Номер 20(6), С. 651 - 675

Опубликована: Май 3, 2024

Язык: Английский

---

Aggregation of rhodopsin mutants in mouse models of autosomal dominant retinitis pigmentosa

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 16, 2024

Abstract Mutations in rhodopsin can cause it to misfold and lead retinal degeneration. A distinguishing feature of these mutants vitro is that they mislocalize aggregate. It unclear whether or not features contribute degeneration observed vivo. The effect P23H G188R misfolding mutations were examined a heterologous expression system knockin mouse models, including model generated here expressing the mutant. In characterizations demonstrate both aggregate, with mutant exhibiting more severe aggregation profile compared potential for aggregate vivo was assessed by PROTEOSTAT, dye labels aggregated proteins. Both photoreceptor cells PROTEOSTAT staining detected surrounding nuclei cells. promotes phenotype greater promoted Here, we show level positive mirrors progression cell death, which suggests role

Язык: Английский

---

The Diverse Roles of Reactive Astrocytes in the Pathogenesis of Amyotrophic Lateral Sclerosis

Brain Sciences, Год журнала: 2024, Номер 14(2), С. 158 - 158

Опубликована: Фев. 4, 2024

Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response pathological stimuli. This process results the loss of typical astrocyte functions acquisition neurotoxic or neuroprotective roles. A growing body research indicates that these astrocytes play a pivotal role pathogenesis amyotrophic lateral sclerosis (ALS), involving calcium homeostasis imbalance, mitochondrial dysfunction, abnormal lipid lactate metabolism, glutamate excitotoxicity, etc. review summarizes characteristics astrocytes, ALS, recent advancements astrocyte-targeting strategies.

Язык: Английский

---

14‐3‐3 Protein‐Protein Interactions: From Mechanistic Understanding to Their Small‐Molecule Stabilization

ChemBioChem, Год журнала: 2024, Номер 25(14)

Опубликована: Май 13, 2024

Abstract Protein‐protein interactions (PPIs) are of utmost importance for maintenance cellular homeostasis. Herein, a central role can be found 14‐3‐3 proteins. These hub‐proteins known to bind hundreds interaction partners, thereby regulating their activity, localization, and/or stabilization. Due ability large variety client proteins, studies protein complexes flourished over the last decades, aiming gain greater molecular understanding these and in health disease. Because crucial within cell, recognized as highly interesting therapeutic targets, encouraging discovery small molecule modulators PPIs. We discuss various examples 14‐3‐3‐mediated regulation its binding partners on mechanistic level, highlighting versatile multi‐functional cell. Furthermore, an overview is given development stabilizers complexes, from initially used natural products fragment‐based approaches. show potential PPI novel agents drug tool compounds 14‐3‐3‐based regulation.

Язык: Английский

---

Mechanisms Underlying Neurodegenerative Disorders and Potential Neuroprotective Activity of Agrifood By-Products

Antioxidants, Год журнала: 2022, Номер 12(1), С. 94 - 94

Опубликована: Дек. 30, 2022

Neurodegenerative diseases, characterized by progressive loss in selected areas of the nervous system, are becoming increasingly prevalent worldwide due to an aging population. Despite their diverse clinical manifestations, neurodegenerative diseases multifactorial disorders with standard features and mechanisms such as abnormal protein aggregation, mitochondrial dysfunction, oxidative stress inflammation. As there no effective treatments counteract increasing interest has been directed potential neuroprotective activities plant-derived compounds found abundantly food agrifood by-products. Food waste extremely negative impact on environment, recycling is needed promote disposal overcome this problem. Many studies have carried out develop green strategies extract bioactive from by-products, peel, leaves, seeds, bran, kernel, pomace, oil cake, investigate biological activity. In review, we focused activity wastes obtained common products widely produced consumed Italy, grapes, coffee, tomatoes, olives, chestnuts, onions, apples, pomegranates.

Язык: Английский

---

Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Авг. 7, 2023

Abstract The AAA + ATPase valosin containing protein (VCP) is essential for cell and organ homeostasis, especially in cells of the nervous system. As part a large network, VCP collaborates with many cofactors to ensure proteostasis under normal, stress, disease conditions. A number mutations have revealed importance human health. In particular, facilitates dismantling aggregates removal dysfunctional organelles. These are critical events prevent malfunction brain other parts line this idea, mutants linked onset progression neurodegeneration diseases. intricate molecular mechanisms that connect distinct pathologies continue be uncovered. Emerging evidence supports model controls cellular functions on multiple levels type specific fashion. Accordingly, derail homeostasis through several can instigate disease. Our review focuses association between neurodegeneration. We discuss latest insights field, emphasize open questions, speculate potential as drug target some most devastating forms

Язык: Английский

---

Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 11, 2024

Abstract Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate impact spaceflight on mouse brain in female mice. Our comparative analysis between ground control spaceflight-exposed animals revealed alterations essential processes including neurogenesis, synaptogenesis synaptic transmission, particularly affecting cortex, hippocampus, striatum neuroendocrine structures. Additionally, observed astrocyte activation signs immune dysfunction. At pathway level, some spaceflight-induced changes exhibit similarities neurodegenerative disorders, marked oxidative stress protein misfolding. integrated serves as stepping stone towards understanding CNS impairments at level individual regions cell types, provides basis comparison future studies. For broader scientific impact, all datasets from study are available through interactive data portal, well National Aeronautics Space Administration (NASA) Open Science Data Repository (OSDR).

Язык: Английский

---