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

Nalidixic acid inhibits the aggregation of HSA: Utilizing the molecular simulations to uncover the detailed insights DOI
Jihad Alrehaili, Razique Anwer, Faizan Abul Qais

et al.

Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: 117, P. 108415 - 108415

Published: Feb. 28, 2025

Language: Английский

Citations

0
Multivalent interaction induces phase separation and formation of more toxic aggregates of α-syn in a yeast model of Parkinson’s disease DOI Creative Commons

Rajeev Jain,

S. K. Sharavanakkumar,

Krishnananda Chattopadhyay

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract The process of protein phase separation, particularly in the context intrinsically disordered proteins, has been extensively studied for its implications several neuro-degenerative diseases. Although mechanism separation and involved molecular grammar have well explored under vitro conditions, focus is now shifting towards developing more complex models order to mimic biological systems closely. Here, we alpha synuclein (α-syn), an whose aggregation implicated pathology Parkinson’s Disease, (PD) inside yeast cells ( Saccharomyces cerevisiae ). Using a positively charged polymer; polyethylenimine (PEI), which binds presumably at negatively C-terminal domain α-syn, find that α-syn can be modulated by least two pathways: one involving second without separation. We further these pathways lead varying fibril characteristics toxicities. believe this model used as quick convenient system screen novel repurposed small molecules against toxic droplets.

Language: Английский

Citations

0
Liquid–liquid phase separation and conformational strains of α-Synuclein: implications for Parkinson’s disease pathogenesis DOI Creative Commons

Eva D. Ruiz-Ortega,

Anna Wilkaniec, Agata Adamczyk

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Oct. 23, 2024

Parkinson’s disease (PD) and other synucleinopathies are characterized by the aggregation deposition of alpha-synuclein ( α -syn) in brain cells, forming insoluble inclusions such as Lewy bodies (LBs) neurites (LNs). The -syn is a complex process involving structural conversion from its native random coil to well-defined secondary structures rich β -sheets, amyloid-like fibrils. Evidence suggests that intermediate species aggregates formed during this responsible for cell death. However, molecular events involved relationship with onset progression remain not fully elucidated. Additionally, clinical pathological heterogeneity observed various has been highlighted. Liquid–liquid phase separation (LLPS) condensate formation have proposed alternative mechanisms could underpin pathology contribute seen synucleinopathies. This review focuses on role cellular environment conformational rearrangement, which may lead existence different strains varying toxicity patterns. discussion will include stress, abnormal LLPS formation, potential pathology.

Language: Английский

Citations

1
Investigation of new non-toxic inhibitors of fibril formation and preservatives for insulin preparations its analogues DOI
Sergei Y. Grishin, Alexey K. Surin, Oxana V. Galzitskaya

et al.

Advances in protein chemistry and structural biology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
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

Citations

0