Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair DOI Creative Commons
С. Н. Ходырева, Nadezhda S. Dyrkheeva, Olga I. Lavrik

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2808 - 2808

Published: Dec. 11, 2024

The nervous system is susceptible to DNA damage and repair defects, if not repaired, neuronal cells can die, causing neurodegenerative diseases in humans. overall picture of what known about mechanisms the still unclear. current challenge use accumulated knowledge basic science on improve treatment disorders. In this review, we summarize understanding function repair, particular, base excision double-strand break pathways as being most important cells. We recent data proteins involved associated with diseases, particular emphasis PARP1 ND-associated proteins, which are have ability undergo liquid–liquid phase separation.

Language: Английский

神经退行性疾病相关淀粉样蛋白的液-液相分离 DOI

Yun-Yi Luo,

Yanmei Li

Chinese Science Bulletin (Chinese Version), Journal Year: 2025, Volume and Issue: 70(7), P. 850 - 859

Published: Feb. 12, 2025

Citations

1
Liquid–liquid phase separation induced by crowding condition affects amyloid-β aggregation mechanism DOI

Ryuki Kobayashi,

Hideki Nabika

Soft Matter, Journal Year: 2024, Volume and Issue: 20(27), P. 5331 - 5342

Published: Jan. 1, 2024

Liquid–liquid phase separation induced by crowding condition affects the localization and fibril formation of amyloid-β.

Language: Английский

Citations

5
Biomolecular condensates and disease pathogenesis DOI
Ke Ruan, Ge Bai, Yanshan Fang

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: 67(9), P. 1792 - 1832

Published: July 17, 2024

Language: Английский

Citations

4
Ncl liquid-liquid phase separation and SUMOylation mediate the stabilization of HIF-1α expression and promote pyroptosis in ischemic hindlimb DOI Creative Commons
Yanli Wang, Weiliang Wu, Xu Yan

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(4), P. 167706 - 167706

Published: Feb. 10, 2025

Language: Английский

Citations

0
Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications DOI Creative Commons
Nurzhan Abdukarimov, Kamilya Kokabi, Jeannette Kunz

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 527 - 527

Published: April 28, 2025

Iron dysregulation has emerged as a pivotal factor in neurodegenerative pathologies, especially through its capacity to promote ferroptosis, unique form of regulated cell death driven by iron-catalyzed lipid peroxidation. This review synthesizes current evidence on the molecular underpinnings focusing how disruptions iron homeostasis interact with key antioxidant defenses, such system Xc−-glutathione-GPX4 axis, tip neurons toward lethal oxidative damage. Building these mechanistic foundations, we explore ferroptosis intersects hallmark pathologies Alzheimer’s disease (AD) and Parkinson’s (PD) examine accumulation vulnerable brain regions may fuel disease-specific protein aggregation neurodegeneration. We further surveyed distinct components highlighting role peroxidation enzymes, mitochondrial dysfunction, recently discovered parallel pathways that either exacerbate or mitigate neuronal death. Finally, discuss insights open new avenues for neuroprotective strategies, including chelation inhibitors. By questions, this seeks clarify state knowledge proposes directions harness modulation intervention.

Language: Английский

Citations

0
Crowder Chain Length Variability and Excluded Volume Effect on the Phase Separation Behavior of Mucin DOI

Komal Kumari,

Anant Singh,

Priyankar Mandal

et al.

The Journal of Physical Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(42), P. 10505 - 10513

Published: Oct. 11, 2024

Phase separation within cellular membranes, a critical process underpinning diverse functions, is significantly influenced by transmembrane proteins. Therefore, elucidating the behavior of protein in its phase-separated state utmost importance. Our study explores mucin milieu, aiming to determine role crowder chain length and excluded volume phase separation. Confocal microscopy images demonstrate strong partitioning into condensed hydrophobic electrostatic interactions. Fluorescence recovery after photobleaching analysis revealed increased mobility presence shorter crowders, indicating dynamic phases. Excluded calculation using theoretical model emphasizes importance under crowded conditions. findings underscore ability phase-separate conditions, highlighting crucial enhancing our understanding involvement cancer progression.

Language: Английский

Citations

3
Surface-catalyzed liquid–liquid phase separation and amyloid-like assembly in microscale compartments DOI Creative Commons
Giuseppe De Luca, Giuseppe Sancataldo, Benedetto Militello

et al.

Journal of Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 676, P. 569 - 581

Published: July 18, 2024

Liquid-liquid phase separation is a key phenomenon in the formation of membrane-less structures within cell, appearing as liquid biomolecular condensates. Protein condensates are most studied for their biological relevance, and tendency to evolve, resulting aggregates with high level order called amyloid. In this study, it demonstrated that Human Insulin forms micrometric, round amyloid-like at room temperature sub-microliter scale aqueous compartments. These distinctive particles feature solid core enveloped by fluid-like corona form interface between compartment glass coverslip upon which they cast. Quantitative fluorescence microscopy used study real-time superstructures. Their results driven liquid–liquid process arises from spatially heterogeneous distribution nuclei glass-water interface. The proposed experimental setup allows modifying surface-to-volume ratio compartments, affects aggregation rate particle size, while also inducing fine alterations molecular final assemblies. findings enhance understanding factors governing amyloid structure formation, shedding light on catalytic role surfaces process.

Language: Английский

Citations

2
Implications of liquid-liquid phase separation and ferroptosis in Alzheimer's disease DOI
Fu-Wei Wang, Zihao Chen, Qiong Zhou

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 259, P. 110083 - 110083

Published: July 21, 2024

Language: Английский

Citations

1
TDP-43 Amyloid Fibril Formation via Phase Separation-Related and -Unrelated Pathways DOI Creative Commons
Pin‐Han Lin,

Guan-Wei Wu,

Yu‐Hao Lin

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 2, 2024

Intrinsically disordered regions (IDRs) in proteins can undergo liquid-liquid phase separation (LLPS) for functional assembly, but this increases the chance of forming disease-associated amyloid fibrils. Not all fibrils form through LLPS however, and importance relative to other pathways fibril formation remains unclear. We investigated question TDP-43, a motor neuron disease dementia-causing protein that undergoes LLPS, using thioflavin T (ThT) fluorescence, NMR, transmission electron microscopy (TEM), wide-angle X-ray scattering (WAXS) experiments. Using fluorescence probe modified from ThT strategically designed targeting assembly rather than β-sheets supported by TEM images, we propose biphasic signals observed under LLPS-favoring conditions are due presence amorphous aggregates. These aggregates represent an intermediate state diverges direct pathway β-sheet-dominant Under non-LLPS contrast (at low pH or at physiological construct with key residues removed), forms hydrogel. Real-time WAXS data, signals, images collectively demonstrate gelation process circumvents yet still results fibril-like structural networks. suggest IDR TDP-43 disease-causing regardless pathway. Our findings shed light on why both LLPS-promoting LLPS-inhibiting mutants found TDP-43-related diseases.

Language: Английский

Citations

1
A reaction-diffusion model captures the essence of liquid-liquid phase separation DOI Creative Commons
Nayana Mukherjee, Abdul Wasim, Jagannath Mondal

et al.

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

Published: April 30, 2024

In this work we propose the formulation of a continuum model for liquid-liquid phase separation (LLPS) using reaction diffusion framework. We consider well mixed liquid consisting three phases, dense droplet phase, dilute and remaining part to be solvent phase. As key feature, includes both spatial temporal aspects free energy functional between that is physically motivated by reference molecular simulation. The exhaustive numerical simulations captures dynamical formation droplets existence LLPS. time progresses, simulation reveal smaller gradually vanish, single undergoes continuous growth until it reaches stable size. predicts extent diffusivity as their mutual interaction would modulate kinetics formation. Finally show introduction fluctuation in accelerate process.

Language: Английский

Citations

0