Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4368 - 4368

Published: April 15, 2024

Dynamic regulation of the cellular proteome is mainly controlled in endoplasmic reticulum (ER). Accumulation misfolded proteins due to ER stress leads activation unfolded protein response (UPR). The primary role UPR reduce bulk damages and try drive back system former or a new homeostatic state by autophagy, while an excessive level results apoptosis. It has already been proven that proper order characteristic features both surviving self-killing mechanisms are negative positive feedback loops, respectively. suggest these loops found not only within but also between branches UPR, fine-tuning stress. In this review, we summarize recent knowledge dynamical mechanism using theoretical molecular biological techniques. addition, review pays special attention describing action controlling life-and-death decision upon Since appears diseases common worldwide, more detailed understanding behaviour medical importance.

Language: Английский

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Understanding of Alzheimer's Disease Pathophysiology for Therapeutic Implications of Natural Products as Neuroprotective Agents

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102680 - 102680

Published: Feb. 1, 2025

Language: Английский

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Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 1, 2025

ABSTRACT Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions individuals. These characterized by pathological changes in various brain regions, specific genetic mutations associated with disease, deposits abnormal proteins, degeneration neurological cells. As neurodegenerative disorders vary their epidemiological characteristics vulnerability neurons, treatment these is usually aimed at slowing disease progression. The heterogeneity environmental factors involved process neurodegeneration makes current methods inadequate. However, existence common molecular mechanisms pathogenesis may allow development new targeted therapeutic strategies. Oxidative nitrosative stress damages membrane components accumulating ROS RNS disrupting redox balance. This results induction apoptosis, which important through oxidative stress. Studies conducted using postmortem human samples, animal models, cell cultures demonstrated stress, apoptosis crucial such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, Huntington's disease. excessive production reactive oxygen nitrogen species, elevated levels free radicals, heightened mitochondrial disturbances energy metabolism, oxidation nitrosylation cellular macromolecules recognized triggers neuronal death. Challenges managing treating require better understanding this field level. Therefore, review elaborates apoptosis.

Language: Английский

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The Interplay Between Endoplasmic Reticulum Stress and Ferroptosis in Neurological Diseases

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Feb. 10, 2025

Language: Английский

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The Potential of Mitochondrial Therapeutics in the Treatment of Oxidative Stress and Inflammation in Aging

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Language: Английский

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Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(16), P. 2966 - 2981

Published: July 31, 2024

Sinapic acid (SA) is a phenylpropanoid derivative found in various natural sources that exhibits remarkable versatile properties, including antioxidant, anti-inflammatory, and metal-chelating capabilities, establishing itself as promising candidate for the prevention treatment of conditions affecting central nervous system, such Alzheimer's disease (AD), Parkinson's (PD), ischemic stroke, other neurological disorders. These effects also include neuroprotection epilepsy models, evidenced by reduction seizure-like behavior, cell death specific hippocampal regions, lowered neuroinflammatory markers. In AD, SA enhances memory, reverses cognitive deficits, attenuates astrocyte activation. has positive on cognition improving memory lowering oxidative stress. This shown lower levels stress markers, higher antioxidant enzyme activity, better retention. Additionally, stroke PD provides microglial protection exerts anti-inflammatory effects. review emphasizes SA's multifaceted neuroprotective properties its potential role brain Despite need further research to fully understand mechanisms action clinical applicability, stands out valuable bioactive compound ongoing quest combat neurodegenerative diseases enhance quality life affected individuals.

Language: Английский

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Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1062 - 1062

Published: Aug. 30, 2024

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration structure and function nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's (AD), Huntington's (HD), Amyotrophic lateral sclerosis (ALS), Multiple (MS), often lead to severe cognitive motor deficits. A critical component neurodegenerative pathologies is imbalance between pro-oxidant antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption lipid-rich environment make it particularly vulnerable damage. Pro-oxidants such as reactive nitrogen species (RNS) (ROS) are continuously generated during normal metabolism, counteracted enzymatic non-enzymatic defenses. In diseases, this balance disrupted, leading neuronal This systematic review explores roles stress, gut microbiota, epigenetic modifications aiming elucidate interplay these factors identify potential therapeutic strategies. We conducted comprehensive search articles published 2024 across major databases, focusing on studies examining relationships redox homeostasis, changes neurodegeneration. total 161 were included, comprising clinical trials, observational studies, experimental research. Our findings reveal that stress plays central role pathogenesis with microbiota composition significantly influencing balance. Specific bacterial taxa markers identified modulators suggesting novel avenues for intervention. Moreover, recent evidence from human animal supports emerging concept targeting homeostasis through therapies. Future research should focus validating targets settings exploring personalized medicine strategies based individual profiles.

Language: Английский

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A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 53 - 53

Published: Jan. 5, 2025

Investigating amyloid-β (Aβ) peptides in solution is essential during the initial stages of developing lead compounds that can influence Aβ fibrillation while peptide still a soluble state. The tendency Aβ(1-42) to misfold solution, correlated aetiology Alzheimer's disease (AD), one main hindrances characterising its aggregation kinetics cell-mimetic environment. Moreover, triggers unfolded protein response (UPR) endoplasmic reticulum (ER), leading cellular dysfunction and multiple cell death modalities, exacerbated by reactive oxygen species (ROS), which damage components trigger inflammation. Antioxidants like curcumin, derivative Curcuma longa, help mitigate ER stress scavenging ROS enhancing antioxidant enzymes. Furthermore, evidence literature highlights effect curcumin on secondary structure Aβ(1-42). This explorative study investigates conformational behaviour presence six derivatives using circular dichroism (CD) explore their interactions with lipid bilayers, potentially preventing aggregate formation. results suggest synthetic tetrahydrocurcumin (THC) interacts amyloid all systems presented, cyclocurcumin (CYC) bisdemethoxycurcumin (BMDC) only interact when less stable conformation. Molecular dynamics simulations helped visualise curcuminoids' an aqueous system hypothesise importance surface exposition solvent, differently modulated derivatives.

Language: Английский

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Understanding the neurobiological mechanisms of LPS‑induced memory impairment

Acta Neurobiologiae Experimentalis, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

In recent years, growing evidence suggests that lipopolysaccharide (LPS), a bacterial endotoxin found in the outer membrane of gram‑negative bacteria, can influence cognitive functions, particularly memory formation and retrieval. However, underlying mechanisms through which LPS exerts its effects on remain incompletely understood. This review used various electronic databases, including PubMed, Scopus, Web Science, to identify relevant studies published between 2000 2024. Articles were selected based their focus LPS‑induced impairments, experimental models, molecular pathways, neurochemical alterations. administration has been consistently shown disrupt processes both animals humans, although magnitude duration impairments might vary depending factors such as dose, timing, context exposure. Several potential have proposed explain deficits, neuroinflammation, alterations synaptic plasticity, disruption neurotransmitter systems, dysfunction blood‑brain barrier. Moreover, activate immune signaling toll‑like receptors, interleukins, microglia, further contribute impairments. Such insights may pave way for development targeted therapeutic interventions aimed at ameliorating deficits associated with conditions involving exposure, infections, sepsis, neuroinflammatory disorders.

Language: Английский

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Unlocking the Neuroprotective Potential of Silymarin: A Promising Ally in Safeguarding the Brain from Alzheimer’s Disease and Other Neurological Disorders

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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