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

Exploration of neuroscience, Год журнала: 2025, Номер 4

Опубликована: Март 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.

Язык: Английский

Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment DOI Creative Commons
Russel J. Reıter, Ramaswamy Sharma, Walter Manucha

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102480 - 102480

Опубликована: Сен. 3, 2024

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.

Язык: Английский

Процитировано

12
Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids DOI Creative Commons
Doris Loh, Russel J. Reıter

Exploration of neuroscience, Год журнала: 2025, Номер 4

Опубликована: Март 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.

Язык: Английский

Процитировано

0