Application of Optogenetics in Neurodegenerative Diseases DOI Creative Commons
Qian Zhang, Tianjiao Li, Mengying Xu

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: July 26, 2024

Abstract Optogenetics, a revolutionary technique integrating optical and genetic methodologies, offers unparalleled precision in spatial targeting temporal resolution for cellular control. This approach enables the selective manipulation of specific neuronal populations, inducing subtle electrical changes that significantly impact complex neural circuitry. As optogenetics precisely targets modulates activity, it holds potential significant breakthroughs understanding potentially altering course neurodegenerative diseases, characterized by loss leading to functional deficits within nervous system. The integration into disease research has advanced field, offering new insights paving way innovative treatment strategies. Its application clinical settings, although still nascent stages, suggests promising future addressing some most challenging aspects disorders. In this review, we provide comprehensive overview these undertakings.

Language: Английский

Tau interactome and RNA binding proteins in neurodegenerative diseases DOI Creative Commons
Tomas Kavanagh, Aditi Halder, Eleanor Drummond

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Oct. 17, 2022

Pathological tau aggregation is a primary neuropathological feature of many neurodegenerative diseases. Intriguingly, despite the common presence aggregates in these diseases affected brain regions, clinical symptoms, and morphology, conformation, isoform ratio present varies widely. The tau-mediated disease mechanisms that drive are still unknown. Tau interactome studies critically important for understanding tauopathy. They reveal interacting partners define pathways, interactions provide potential insight into cellular environment protein during pathological aggregation. Here we combined analysis 12 human tissue, cell culture models rodent disease. Together, identified 2084 proteins interact with tissue 1152 Our revealed consistent enrichment between involved RNA binding, ribosome, proteasome function. Comparison substantial differences two species. We also performed second to identify enriched neurons containing granulovacuolar degeneration or neurofibrillary tangle pathology. These results timed dysregulation as pathology develops. binding proteins, particularly HNRNPs, emerged early disease-associated interactors therefore may have an role driving

Language: Английский

Citations

60
Identification of circRNAs linked to Alzheimer's disease and related dementias DOI Creative Commons

Sambhavi Puri,

Junming Hu,

Zhuorui Sun

et al.

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 19(8), P. 3389 - 3405

Published: Feb. 16, 2023

Abstract Introduction Circular RNAs (circRNAs) exhibit selective expression in the brain and differential regulation Alzheimer's disease (AD). To explore role of circRNAs AD, we investigated how circRNA varies between regions with AD‐related stress human neuronal precursor cells (NPCs). Methods Ribosomal RNA–depleted hippocampus RNA‐sequencing data were generated. Differentially regulated AD related dementias detected using CIRCexplorer3 limma. results validated quantitative real‐time PCR cDNA from NPCs. Results We identified 48 that significantly associated AD. observed differed by dementia subtype. Using NPCs, demonstrated exposure to oligomeric tau elicits downregulation similar brain. Discussion Our study shows can vary subtype region. also be AD‐linked independently their cognate linear messenger (mRNAs).

Language: Английский

Citations

25
Role of N6-methyladenosine modification in central nervous system diseases and related therapeutic agents DOI Creative Commons
Junya Lv, Lijuan Xing, Xin Zhong

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114583 - 114583

Published: March 28, 2023

N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. methylation RNA associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's (PD), depression, cerebral apoplexy, brain injury, epilepsy, arteriovenous malformations, glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns therapeutic areas disorders. Here, we mainly summarized role diseases potential drugs. The aim this review expected to be useful systematically assess as new biomarker develop innovative modulators for amelioration treatment

Language: Английский

Citations

24
CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis DOI Creative Commons

Avi J. Samelson,

Nabeela Ariqat, Justin McKetney

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 17, 2023

Aggregation of the protein tau defines tauopathies, which include Alzheimer's disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to aggregation subsequent dysfunction death, but underlying mechanisms unknown. To systematically uncover cellular factors controlling accumulation aggregates in human neurons, we conducted a genome-wide CRISPRi-based modifier screen iPSC-derived neurons. The uncovered expected pathways, including autophagy, also unexpected UFMylation GPI anchor synthesis. We discover that E3 ubiquitin ligase CUL5

Language: Английский

Citations

24
The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders DOI
Bess Frost, Josh Dubnau

Annual Review of Neuroscience, Journal Year: 2024, Volume and Issue: 47(1), P. 123 - 143

Published: April 25, 2024

Over 40% of the human genome is composed retrotransposons, DNA species that hold potential to replicate via an RNA intermediate and are evolutionarily related retroviruses. Retrotransposons most studied for their ability jump within a genome, which can cause damage novel insertional mutations. Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, extrachromosomal circular DNAs, also be potent activators innate immune system. A growing body evidence suggests retrotransposons activated in age-related neurodegenerative disorders such activation causally contributes neurotoxicity. Here we provide overview retrotransposon biology outline disorders, with emphasis on those involving TAR-DNA binding protein-43 (TDP-43) tau. Studies date basis ongoing clinical trials promise innovative strategies ameliorate adverse effects dysregulation disorders.

Language: Английский

Citations

8
Intracellular tau fragment droplets serve as seeds for tau fibrils DOI
Yoshiyuki Soeda, Hideaki� Yoshimura, Hiroko Bannai

et al.

Structure, Journal Year: 2024, Volume and Issue: 32(10), P. 1793 - 1807.e6

Published: July 19, 2024

Language: Английский

Citations

8
Gut microbe-derived betulinic acid alleviates sepsis-induced acute liver injury by inhibiting macrophage NLRP3 inflammasome in mice DOI Creative Commons

Xuheng Tang,

Tao Zeng, Wenyan Deng

et al.

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Sepsis-induced acute liver injury (SALI) is a prevalent and life-threatening complication associated with sepsis. The gut microbiota plays crucial role in the maintenance of health development diseases. impact physical exercise on modulation has been well-documented. However, potential microbiome training-induced protection against SALI remains uncertain. Here, we discovered training ameliorated systemic inflammation septic mice. Notably, pre-depletion abolished protective effects Fecal transplantation treatment revealed that training-associated contributed to beneficial effect SALI. Exercise modulated metabolism Ligilactobacillus enriched betulinic acid (BA) levels Functionally, BA conferred by inhibiting hepatic inflammatory response bound inactivated hnRNPA2B1, thus suppressing NLRP3 inflammasome activation macrophages. Collectively, this study reveals involved SALI, microbiota-derived inhibits via hnRNPA2B1-NLRP3 axis, providing therapeutic strategy for Sepsis characterized dysregulated immune an infection leads multiple organ dysfunction. occurrence frequently observed during initial stage sepsis directly linked mortality intensive care unit. preventive well recognized, yet underlying mechanism poorly elucidated. alters mice, increasing abundance promoting generation BA. Additionally, supplementation can suppress macrophages binding thereby mitigating These results highlight response, which represents stride toward implementing microbiome-based strategies clinical management

Language: Английский

Citations

1
RNA induces unique tau strains and stabilizes Alzheimer’s disease seeds DOI Creative Commons
Amy N. Zwierzchowski-Zarate, Aydé Mendoza‐Oliva,

Omar M. Kashmer

et al.

Journal of Biological Chemistry, Journal Year: 2022, Volume and Issue: 298(8), P. 102132 - 102132

Published: June 11, 2022

Tau aggregation underlies neurodegenerative tauopathies, and transcellular propagation of tau assemblies unique structure, i.e., strains, may underlie the diversity these disorders. Polyanions have been reported to induce in vitro, but precise trigger convert from an inert a seed-competent form disease states is unknown. RNA triggers fibril formation vitro has observed associate with neurofibrillary tangles human brain. Here, we tested whether exerts sequence-specific effects on assembly strain formation. We found that three homopolymers, polyA, polyU, polyC, all bound tau, only polyA triggered seed In addition, polyA:tau seeds fibrils were sensitive RNase. also origin influenced ability adopt structure would stable strains. Human potently induced created conformations preferentially formed strains HEK293T cell model, whereas other sources, or heparin, produced not stably maintained cultured cells. Finally, soluble, insoluble Alzheimer's brain conclude specifically induces dominant pathological propagate possibly tauopathies.

Language: Английский

Citations

33
N6‐methyladenosine (m6A) modification in gynecological malignancies DOI
Chunmei Zhang, Ning Liu

Journal of Cellular Physiology, Journal Year: 2022, Volume and Issue: 237(9), P. 3465 - 3479

Published: July 8, 2022

N6-methyladenosine (m6A) modification is one of the most abundant modifications in eukaryotic mRNA, regulated by m6A methyltransferase and demethylase. modified RNA specifically recognized bound recognition proteins, which mediate splicing, maturation, exonucleation, degradation, translation. In gynecologic malignancies, modification-related molecules are expressed aberrantly, significantly altering posttranscriptional methylation level target genes their stability. The also regulates related metabolic pathways, thereby controlling tumor development. This review analyzes composition mode action proteins biological functions malignant progression provide new ideas for early clinical diagnosis targeted therapy malignancies.

Language: Английский

Citations

30
Neuronal nuclear tau and neurodegeneration DOI Creative Commons
Alejandro Antón‐Fernández, Laura Vallés‐Saiz, Jesús Ávila

et al.

Neuroscience, Journal Year: 2022, Volume and Issue: 518, P. 178 - 184

Published: July 22, 2022

Tau is a well-known microtubule-associated protein related to its cytoplasmic localization in neuronal cell. However, tau has been located at the cell nucleus where it could be nucleic acid-associated by preferential binding DNA sequences present nucleolus and pericentromeric heterochromatin. This less of not trivial, since during aging, an increase amount nuclear takes place may described role activation transposons further aging acceleration.

Language: Английский

Citations

28