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

RNA modifications: importance in immune cell biology and related diseases DOI Creative Commons
Lian Cui, Rui Ma,

Jiangluyi Cai

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

Citations

197
Tau liquid–liquid phase separation in neurodegenerative diseases DOI Creative Commons
Solomiia Boyko, Witold K. Surewicz

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 32(7), P. 611 - 623

Published: Feb. 15, 2022

Language: Английский

Citations

112
The IGF2BP family of RNA binding proteins links epitranscriptomics to cancer DOI Creative Commons
Deepthi Ramesh, Sònia Guil

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 18 - 31

Published: May 25, 2022

RNA binding proteins that act at the post-transcriptional level display a richness of mechanisms to modulate transcriptional output and respond changing cellular conditions. The family IGF2BP recognize mRNAs modified by methylation lengthen their lifecycle in context stable ribonucleoprotein particles promote cancer progression. They are emerging as key 'reader' epitranscriptomic field, driving fate bound substrates under physiological disease Recent developments field include recognition noncoding play crucial roles mediating pro-growth features family, not only regulated targets, but also modulators function themselves. In this review, we summarize regulatory link molecular role m6A modification readers phenotype, thus providing comprehensive insight into function.

Language: Английский

Citations

73
RNA methylation influences TDP43 binding and disease pathogenesis in models of amyotrophic lateral sclerosis and frontotemporal dementia DOI Creative Commons

Michael McMillan,

Nicolás Gómez,

Caroline Hsieh

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(2), P. 219 - 236.e7

Published: Jan. 1, 2023

Language: Английский

Citations

59
Conserved reduction of m 6 A RNA modifications during aging and neurodegeneration is linked to changes in synaptic transcripts DOI Creative Commons

Ricardo Castro-Hernández,

Tea Berulava,

Mariia Metelova

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(9)

Published: Feb. 22, 2023

N 6 -methyladenosine (m A) regulates mRNA metabolism. While it has been implicated in the development of mammalian brain and cognition, role m A synaptic plasticity, especially during cognitive decline, is not fully understood. In this study, we employed methylated RNA immunoprecipitation sequencing to obtain epitranscriptome hippocampal subregions CA1, CA3, dentate gyrus anterior cingulate cortex (ACC) young aged mice. We observed a decrease levels animals. Comparative analysis (CC) tissue from cognitively intact human subjects Alzheimer’s disease (AD) patients showed decreased methylation AD patients. changes common brains mice were found transcripts linked function including calcium/calmodulin-dependent protein kinase 2 ( CAMKII ) AMPA-selective glutamate receptor 1 Glua1 ). used proximity ligation assays show that reduced result synthesis as exemplified by GLUA1. Moreover, impaired function. Our results suggest controls may play decline associated with aging AD.

Language: Английский

Citations

42
The six brain‐specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes DOI Creative Commons
Sarah Buchholz, Hans Zempel

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(5), P. 3606 - 3628

Published: March 31, 2024

Alternative splicing of the human MAPT gene generates six brain-specific TAU isoforms. Imbalances in isoform ratio can lead to neurodegenerative diseases, underscoring need for precise control over balance. Tauopathies, characterized by intracellular aggregates hyperphosphorylated TAU, exhibit extensive neurodegeneration and be classified isoforms present pathological accumulations.

Language: Английский

Citations

20
Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

Citations

16
RNA dysregulation in neurodegenerative diseases DOI Creative Commons
Yini Li, Shuying Sun

The EMBO Journal, Journal Year: 2025, Volume and Issue: 44(3), P. 613 - 638

Published: Jan. 9, 2025

Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying underscore the essential role regulation maintaining neuronal health function. molecules are bound by RNA-binding proteins (RBPs), interactions between RNAs RBPs commonly affected In this review, we highlight progress understanding dysregulated RNA-processing pathways causes RBP dysfunction across various neurodegenerative diseases. We discuss both established emerging RNA-mediated neuropathogenesis rapidly evolving field. Furthermore, explore development potential RNA-targeting therapeutic approaches for treatment

Language: Английский

Citations

3
Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification DOI Creative Commons
Thai B. Nguyen, Ricardo Miramontes,

Carlos Chillón-Marinas

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Language: Английский

Citations

2
VCP regulates early tau seed amplification via specific cofactors DOI Creative Commons
Sushobhna Batra, Jaime Vaquer-Alicea,

Clarissa Valdez

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 7, 2025

Abstract Background Neurodegenerative tauopathies may progress based on seeding by pathological tau assemblies, whereby an aggregate is released from one cell, gains entry to adjacent or connected and serves as a specific template for its own replication in the cytoplasm. Seeding into complex cytoplasmic milieu happens within hours, implying existence of unknown factors that regulate this process. Methods We used proximity labeling identify proteins control seed amplification 5 h exposure. fused split-APEX2 C-terminus repeat domain (RD) reconstitute peroxidase activity after seeded intracellular aggregation. Valosin containing protein (VCP/p97) was top hit. VCP harbors dominant mutations underlie two neurodegenerative diseases, multisystem proteinopathy vacuolar tauopathy, but mechanistic role unclear. immortalized cells human neurons study effects seeding. exposed fibrils brain homogenates cell culture media measured uptake induction aggregation following various genetic pharmacological manipulations VCP. Results knockdown reduced Chemical inhibitors had opposing HEK293T biosensor neurons: ML-240 increased efficiency, whereas NMS-873 decreased it. The only functioned when administered 8 exposure, indicating early processing. screened 30 co-factors knockout knockdown. Reduction ATXN3, NSFL1C, UBE4B, NGLY1, OTUB1 seeding, did NPLOC4, which also uniquely soluble levels. By contrast, reduction FAF2 Conclusions Divergent chemical cofactor indicate regulates This consistent with processing centered directs seeds acutely towards degradation vs. amplification.

Language: Английский

Citations

2