In-silico assessment of the potential impact of missense SNPs in SYNE4 and SUN1 on the LINC complex and their association with hearing loss DOI Open Access
Madoussou Toure, Salaheddine Redouane, Hicham Charoute

et al.

Human Gene, Journal Year: 2023, Volume and Issue: 39, P. 201244 - 201244

Published: Dec. 4, 2023

Language: Английский

Mechanism and role of nuclear laminin B1 in cell senescence and malignant tumors DOI Creative Commons

Tingcong Lv,

Cong Wang, Jialin Zhou

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: June 1, 2024

Nuclear lamin B1 (LMNB1) is a member of the nuclear protein family. LMNB1 can maintain and ensure stability structure influence process cell senescence by regulating chromatin distribution, DNA replication transcription, gene expression, cycle, etc. In recent years, several studies have shown that abnormal expression LMNB1, classical biomarker senescence, highly correlated with progression various malignant tumors; therefore considered new potential tumor marker therapeutic target. However, mechanism action influenced many factors, which are difficult to clarify at present. This article focuses on progress in understanding role tumors offers insights could contribute elucidating provide direction for further research.

Language: Английский

Citations

10

Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation DOI

Jagdish Mishra,

Subhajit Chakraborty,

Niharika Niharika

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 12, 2024

Abstract Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in cell's physical surroundings. These of impose mechanical tension intracellular protein network (both cytosolic nuclear). could released by series protein–protein interactions often facilitated membrane lipids, lectins sugar molecules thus generate type signal drive cellular processes, including differentiation, polarity, growth, adhesion, movement, survival. Recent experimental data have accentuated molecular mechanism this transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins plasma discern channel information interior. Cells respond message altering their arrangement directly transmitting nucleus through connection cytoskeleton nucleoskeleton before despatched biochemical signaling pathways. Nuclear transmission force leads activation chromatin modifiers modulation epigenetic landscape, inducing reorganization gene expression regulation; time chemical messengers (transcription factors) arrive into nucleus. While significant research has been done on role mechanotransduction tumor development cancer progression/metastasis, mechanistic basis force‐activated carcinogenesis is still enigmatic. Here, review, we discussed various cues connections better comprehend also explored detailed some multiple players (proteins macromolecular complexes) involved Thus, described an avenue: how stress directs modulate epigenome cells aberrant phenotype.

Language: Английский

Citations

9

Altered nuclear envelope homeostasis is a key pathogenic event in C9ORF72-linked ALS/FTD DOI Open Access
Riccardo Sirtori,

Michelle Gregoire,

Alicia Collins

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 4, 2024

SUMMARY ALS and FTD are complex neurodegenerative disorders that primarily affects motor neurons in the brain spinal cord, cortical frontal lobe. Although pathogenesis of ALS/FTD is unclear, recent research spotlights nucleocytoplasmic transport impairment, DNA damage, nuclear abnormalities as drivers neuronal death. In this study, we show loss envelope (NE) integrity a key pathology associated with pore (NPC) injury C9ORF72 mutant neurons. Importantly, mechanical stresses generated by cytoskeletal forces on NE can lead to NPC injury, integrity, accumulation damage. demonstrate restoring tensional homeostasis, disconnecting nucleus from cytoskeleton, rescue reduce damage cells. Together, our data suggest modulation homeostasis repair may represent novel promising therapeutic target for ALS/FTD.

Language: Английский

Citations

6

The Role of the LINC Complex in Ageing and Microgravity DOI Creative Commons

Ivana Lansweers,

Sharon van Rijthoven,

Jack J. W. A. van Loon

et al.

Mechanisms of Ageing and Development, Journal Year: 2025, Volume and Issue: unknown, P. 112028 - 112028

Published: Jan. 1, 2025

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex plays a crucial role in connecting the nuclear envelope to cytoskeleton, providing structural support nucleus facilitating mechanical signaling between extracellular environment nucleus. Research mechanobiology onboard International Space Station (ISS) simulated microgravity (SMG) highlight importance gravity functional mechanotransduction. Although altered research regarding has been greatly focused on cytoskeleton matrix (ECM), recent demonstrates that SMG also induces changes mechanics gene expression patterns, which have shown be LINC dependent. Additionally, dysregulation disrupts integrity leads shape abnormalities both Hutchinson-Gilford Progeria Syndrome (HGPS) aged cells, highlights significance related proteins ageing age-related disorders. Interestingly, as effects spaceflight closely resemble those found elderly, seems induce an accelerated phenotype astronauts. Therefore, this review will explore microgravity, further elucidate interplay loss gravitational loading ageing.

Language: Английский

Citations

0

Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke DOI Open Access
Júlia Baixauli-Martín, Marı́a C. Burguete, Mikahela A. López‐Morales

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2364 - 2364

Published: March 6, 2025

In recent years, evidence of the existence cellular senescence in central nervous system has accumulated. ischemic stroke, been suggested as an unidentified pathophysiological mechanism, prompting research into neuroprotective potential senolytic drugs. This study aims to provide spatio-temporal brain following stroke and elucidate involved pathways cell types. We focused on most established markers senescence: cycle arrest (p16, p21); lysosomal activity (senescence-associated β-galactosidase [SA-β-gal]); senescence-associated secretory phenotype ([SASP]; Interleukin-6 [IL-6], Interleukin-1β [IL-1β], Tumor necrosis factor [TNF]); DNA/nuclear damage (Checkpoint kinase 1 [Chk1], Checkpoint 2 [Chk2], Lamin B1 [LB1]). Male Wistar rats underwent 60 min transient middle cerebral artery occlusion, followed by 24 h 3, 7, 14 days recovery. Our results show significant increases p16 expression, particularly neurons microglia/macrophages; SA-β-gal accumulation infarcted tissue; SASP early after reperfusion; changes Chk1, Chk2, LB1 at days. Overall, our findings lend support microglia/macrophages. However, there is still room gain further insight role pathophysiology implementation successful therapy.

Language: Английский

Citations

0

Transiently formed nucleus-to-cilium microtubule arrays mediate senescence initiation in a KIFC3-dependent manner DOI Creative Commons

Jielu Hao Robichaud,

Yingyi Zhang, Chuan Chen

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 12, 2024

Despite the importance of cellular senescence in human health, how damaged cells undergo remains elusive. We have previously shown that promyelocytic leukemia nuclear body (PML-NBs) translocation ciliary FBF1 is essential for induction stressed cells. Here we discover an early event occurring transient assembly stress-induced nucleus-to-cilium microtubule arrays (sinc-MTs). The sinc-MTs are distinguished by unusual polyglutamylation and unique polarity, with minus-ends nucleating near envelope plus-ends base. KIFC3, a minus-end-directed kinesin, recruited to interacts centrosomal protein CENEXIN1. In cells, CENEXIN1 co-translocates PML-NBs. Deficiency KIFC3 abolishes PML-NB CENEXIN1, as well initiation Our study reveals KIFC3-mediated transport along polyglutamylated prerequisite mammalian

Language: Английский

Citations

2

Apoptosis-induced translocation of nesprin-2 from the nuclear envelope to mitochondria is associated with mitochondrial dysfunction DOI Creative Commons

Hila Zohar,

Liora Lindenboim,

Oren Gozlan

et al.

Nucleus, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 15, 2024

Accumulating evidence suggests that the nuclear envelope (NE) is not just a target, but also mediator of apoptosis. We showed recently NE protein nesprin-2 has pro-apoptotic activity, which involves its subcellular redistribution and Bcl-2 proteins. Here we further characterize activity focusing on redistribution. assessed kinetics endogenous tagged with GFP relative to apoptosis-associated mitochondrial dysfunction. The results show apoptosis-induced GFP-nesprin-2G occurred by two different modes - complete partial, both lead appearance nesprin-2G near mitochondria. Moreover, GFP-nesprin-2 associated reduction in membrane potential outer permeabilization precedes morphological features Our translocation mitochondria an early apoptotic effect dysfunction, may be responsible for function nesprin-2.

Language: Английский

Citations

0

Unraveling the nexus of nesprin in dilated cardiomyopathy: From molecular insights to therapeutic prospects DOI

Qin Qin,

Ziyi Zhou, Y.-X. Liu

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 358, P. 123126 - 123126

Published: Oct. 11, 2024

Language: Английский

Citations

0

Diverse Roles of the LINC Complex in Cellular Function and Disease in the Nervous System DOI Open Access
Ken-ichiro Kuwako,

Sadafumi Suzuki

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11525 - 11525

Published: Oct. 26, 2024

The linker of nucleoskeleton and cytoskeleton (LINC) complex, which spans the nuclear envelope, physically connects components to plays a pivotal role in various cellular processes, including positioning, cell migration, chromosomal configuration. Studies have revealed that LINC complex is essential for different aspects nervous system, particularly during development. significance neural lineage cells further corroborated by fact mutations genes associated with been implicated several neurological diseases, neurodegenerative psychiatric disorders. In this review, we aimed summarize expanding knowledge complex-related neuronal functions diseases.

Language: Английский

Citations

0

In-silico assessment of the potential impact of missense SNPs in SYNE4 and SUN1 on the LINC complex and their association with hearing loss DOI Open Access
Madoussou Toure, Salaheddine Redouane, Hicham Charoute

et al.

Human Gene, Journal Year: 2023, Volume and Issue: 39, P. 201244 - 201244

Published: Dec. 4, 2023

Language: Английский

Citations

0