Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids DOI Creative Commons
Doris Loh, Russel J. Reıter

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: 4

Published: March 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Language: Английский

Structural insights and milestones in TDP-43 research: A comprehensive review of its pathological and therapeutic advances DOI Creative Commons
Mei Dang, Longjiang Wu, Xiaoying Zhang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 141677 - 141677

Published: March 1, 2025

Transactive response (TAR) DNA-binding protein 43 (TDP-43) is a critical RNA/DNA-binding involved in various cellular processes, including RNA splicing, transcription regulation, and stability. Mislocalization aggregation of TDP-43 the cytoplasm are key features pathogenesis several neurodegenerative diseases, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD). This review provides comprehensive retrospective prospective analysis research, highlighting structural insights, significant milestones, evolving understanding its physiological pathological functions. We delineate five major stages from initial discovery as hallmark neurodegeneration to recent advances liquid-liquid phase separation (LLPS) behavior interactions with processes. Furthermore, we assess therapeutic strategies targeting pathology, categorizing approaches into direct indirect interventions, alongside modulating aberrant LLPS. propose that future research will focus on three areas: polymorphisms for disease-specific therapeutics, exploring dual temporal-spatial modulation TDP-43, advancing nano-therapy. More importantly, emphasize importance TDP-43's functional repertoire at mesoscale, which bridges molecular functions broader offers foundational framework development.

Language: Английский

Citations

1
Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids DOI Creative Commons
Doris Loh, Russel J. Reıter

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: 4

Published: March 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Language: Английский

Citations

0