Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens DOI Creative Commons
Relu Cocoş, Bogdan Ovidiu Popescu

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Dec. 31, 2024

Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize discoveries, we provide comprehensive critical overview architecture concepts, Mendelian inheritance the latest insights omnigenic We explore roles common rare variants, gene-gene gene-environment interactions, epigenetic influences shaping phenotypes. Additionally, emphasize importance layers including genomic, transcriptomic, proteomic, epigenetic, metabolomic elucidating molecular mechanisms underlying neurodegeneration. Special attention is given missing heritability contribution particularly context pleiotropy network pleiotropy. examine application single-cell omics technologies, transcriptome-wide association studies, epigenome-wide studies as key approaches for dissecting at tissue- cell-type levels. Our review introduces OmicPeak Disease Trajectory Model, conceptual framework progression, which integrates across biological time points. This highlights adopting genetics approach unravel diseases. Finally, this emerging holistic exploration intricate landscape aim foundation establishing more architectures diseases, enhancing diagnostic precision, predicting pathogenic mechanisms, refining therapeutic strategies conditions.

Language: Английский

Reactive gliosis in traumatic brain injury: a comprehensive review DOI Creative Commons

Zuzana Amlerova,

Martina Chmelová,

Miroslava Andĕrová

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Language: Английский

Citations

15
Common alterations to astrocytes across neurodegenerative disorders DOI
Aksinya Derevyanko, Tao Tao, Nicola J. Allen

et al.

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 90, P. 102970 - 102970

Published: Jan. 28, 2025

Language: Английский

Citations

0
mitoXplorer 3.0, a web tool for exploring mitochondrial dynamics in single-cell RNA-seq data DOI Creative Commons

Margaux Haering,

Andrea Del Bondio, Hélène Puccio

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169004 - 169004

Published: Feb. 1, 2025

Mitochondria are essential eukaryotic organelles, primarily recognized for their roles in ATP production, cellular metabolism and signalling. It is widely accepted that structure, composition function differ across cell types. However, little known about mitochondrial variability within the same type. A comprehensive understanding of dynamics requires investigation at both, individual type single-cell resolution. Based on our mitoXplorer 2.0 web tool, we introduce 3.0 with new features adapted analysing sequencing data, focusing only mitochondria. We developed a formatting script, scXplorer, which generates compatible files data upload. The script pseudo-bulk transcriptomes types from scRNA-seq enabling differential expression analysis subsequent mitochondria-centric classical interfaces. also creates matrix containing mitochondria-associated genes (mito-genes), can be analysed cell-to-cell novel, interactive interfaces created 3.0: these help to identify sub-clusters based mito-genes offer in-depth subpopulations. demonstrate usability predictive power through transcriptome Spinocerebellar Ataxia Type 1 study. Our identified several processes significantly affected SCA1 Purkinje cells, potentially contributing dysfunction degeneration this disease. MitoXplorer freely available https://mitoxplorer3.ibdm.univ-amu.fr.

Language: Английский

Citations

0
Decoding Microglial Polarization and Metabolic Reprogramming in Neurodegenerative Diseases: Implications for Disease Progression and Therapy DOI Creative Commons
Ran Gao, Ya Gao, Wenting Su

et al.

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

As the resident macrophages of brain, microglia are crucial immune cells specific to central nervous system (CNS). They constantly surveil their surroundings and trigger immunological reactions, playing a key role in various neurodegenerative diseases (ND). illnesses progress, exhibit multiple phenotypes. Traditionally, have been classified into two main phenotypes upon activation: pro-inflammatory M1 polarization anti-inflammatory M2 polarization. However, this classification is now considered overly simplistic, as it unable fully convey intricacy diversity inflammatory response. Immune regulatory factors, such chemokines secreted by microglia, essential for modulating brain development, maintaining neural milieu, orchestrating responses injury, along with subsequent repair processes. recent years, significance metabolic reprogramming both physiological microglial activity ND has also become increasingly recognized. Upon activation-triggered infection, or ND-microglia typically modify processes transitioning from oxidative phosphorylation (OXPHOS) glycolysis. This shift facilitates rapid energy production but may enhance responses. review seeks summarize function involvement ND.

Language: Английский

Citations

0
Pharmacology of Hydrogen Sulfide and Its Donors in Cardiometabolic Diseases DOI Open Access
Hai‐Jian Sun, Qing-Bo Lu, Xuexue Zhu

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(5), P. 846 - 895

Published: June 12, 2024

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition its roles in attenuating oxidative stress inflammatory response, burgeoning research emphasizes significance of H2S regulating proteins via persulfidation, well-known modification intricately associated pathogenesis CMDs. This review seeks investigate recent updates on physiological actions endogenous donors addressing diverse aspects CMDs across cellular, animal, clinical studies. Of note, advanced methodologies including multi-omics, intestinal microflora analysis, organoid single-cell sequencing techniques gaining traction due their ability offer comprehensive insights into biomedical research. These emerging approaches hold promise characterizing health diseases. We will critically assesse current literatures clarify while also delineating opportunities challenges they present H2S-based pharmacotherapy Significance Statement The covers developments biology pharmacology Endogenous show great management by numerous signaling pathways. emergence new technologies considerably advance translation H2S.

Language: Английский

Citations

2
A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs DOI Creative Commons
Xiaojun Yu, Yuan-Ting Zhao,

Haimiti Abudouaini

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 12, 2024

Language: Английский

Citations

1
Single-Cell Sequencing Technology and Its Application in the Study of Central Nervous System Diseases DOI
Yang Ding,

Yu-Yuan Peng,

Sen Li

et al.

Cell Biochemistry and Biophysics, Journal Year: 2023, Volume and Issue: 82(2), P. 329 - 342

Published: Dec. 22, 2023

Language: Английский

Citations

3
Bibliometric and visual analysis of single-cell multiomics in neurodegenerative disease arrest studies DOI Creative Commons

Jieyan Wang,

Shu‐Qing Wang,

Qingyu Li

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 8, 2024

Background Neurodegenerative diseases are progressive disorders that severely diminish the quality of life patients. However, research on neurodegenerative needs to be refined and deepened. Single-cell polyomics is a technique for obtaining transcriptomic, proteomic, other information from single cell. In recent years, heat single-cell multiomics as an emerging tool brain science has gradually increased. Therefore, aim this study was analyze current status trends studies related application in through bibliometrics. Result A total 596 publications were included bibliometric analysis. Between 2015 2022, number increased annually, with citations increasing significantly, exhibiting fastest rate growth between 2019 2022. The country/region collaboration map shows United States most cumulative citations, China have collaborations. institutions produced greatest articles Harvard Medical School, Skupin, Alexander, Wiendl. Among authors, Heinz had highest output. Mathys, H accumulated authoritative author field. journal Nature Communications published literature keyword analysis reveals lesions (e.g., Alzheimer’s disease, amyloid beta) core foundation Conversely, RNA sequencing, bioinformatics) nerve cells microglia, astrocytes, neural stem cells) hot frontiers specialty. references, article “Single-cell transcriptomic disease” frequently cited (1,146 citations), “Cell types mouse cortex hippocampus revealed by RNA-seq” Conclusion objective employ methods visualize diseases. This will enable us summarize state reveal key hotspots

Language: Английский

Citations

0
Genomics of human neurological disorders DOI

Robert L. Nussbaum

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 173 - 185

Published: Oct. 11, 2024

Language: Английский

Citations

0
The Link Between Paraquat and Demyelination: A Review of Current Evidence DOI Creative Commons
Renata Silva, Ana Filipa Sobral, Ricardo Jorge Dinis‐Oliveira

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(11), P. 1354 - 1354

Published: Nov. 5, 2024

Paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride), a widely used bipyridinium herbicide, is known for inducing oxidative stress, leading to extensive cellular toxicity, particularly in the lungs, liver, kidneys, and central nervous system (CNS), implicated fatal poisonings. Due its biochemical similarities with neurotoxin 1-methyl-4-phenylpyridinium (MPP+), paraquat has been as Parkinson's disease model, although broader neurotoxic effects suggest participation of multiple mechanisms. Demyelinating diseases are conditions characterized by damage myelin sheath neurons. They affect CNS peripheral (PNS), resulting diverse clinical manifestations. In recent years, growing concerns have emerged about impact chronic, low-level exposure herbicides on human health, due agricultural runoff contaminating drinking water sources their presence food. Studies indicate that may significantly myelinating cells, myelin-related gene expression, structure, cause neuroinflammation, potentially contributing demyelination. Therefore, demyelination represent another mechanism neurotoxicity associated paraquat, which requires further investigation. This manuscript reviews potential association between Understanding this link crucial enhancing strategies minimize preserve public health.

Language: Английский

Citations

0