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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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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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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Nobiletin regulates intracellular Ca2+ levels via IP3R and ameliorates neuroinflammation in Aβ42-induced astrocytes

Redox Biology, Journal Year: 2024, Volume and Issue: 73, P. 103197 - 103197

Published: May 16, 2024

Astrocytes are the major glial cells in human brain and provide crucial metabolic trophic support to neurons. The amyloid-β peptide (Aβ) alter morphological functional properties of astrocytes induce inflammation calcium dysregulation, contributing Alzheimer's disease (AD) pathology. Recent studies highlight role Toll-like receptor (TLR) 4/nuclear factor kappa-light-chain-enhancer activated B (NF-κB) signaling inflammation. Reactive oxygen species (ROS) generated due Aβ, apoptosis worsening AD progression. Astrocytic cell surface receptors, such as purinergic receptors (P2Y1 P2Y2), metabotropic glutamate (mGLUR)5, α7 nicotinic acetylcholine (α7nAChR), N-methyl-d-aspartate (NMDARs), have been suggested interact with inositol trisphosphate (IP3R) on endoplasmic reticulum (ER) Ca2+ movement from ER cytoplasm, causing dysregulation. We found that citrus flavonoid nobiletin (NOB) protected primary Aβ42-induced cytotoxicity inhibited TLR4/NF-κB rat astrocytes. NOB was regulate ROS levels through Keap1-Nrf2 pathway. P2Y1, P2Y2, mGLUR5, α7nAChR, NMDARs induced intracellular by activating IP3R regulated them, thereby regulating levels. Molecular docking analysis revealed a possible interaction between regulation. Furthermore, RNA sequencing various NOB-mediated biological pathways, AD-presenilin, AD-amyloid secretase, Wnt pathway, suggesting neuroprotective roles NOB. To conclude, is promising therapeutic agent for works modulating pathology at

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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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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Role of Flavonoids in Mitigating the Pathological Complexities and Treatment Hurdles in Alzheimer's Disease

Phytotherapy Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

With the passage of time, people step toward old age and become more prone to several diseases associated with age. One such is Alzheimer's disease (AD) which results into neuronal damage dementia progression The existing therapeutics has been hindered by various enkindles like less eminent between remote populations, affordability issues toxicity profiles. Moreover, lack suitable therapeutic option further worsens quality life in older population. Developing an efficient intervention cure AD still a challenge for medical fraternity. Recently, alternative approaches attain attention researchers focus on plant-based therapy mitigating AD. In this context, flavonoids gained centrality as feasible treatment modifying neurological deficits. This review mainly focuses pathological facets economic burden Furthermore, we have explored possible mechanism preclinical clinical aspects curing Flavonoids being potential therapeutic, target pathogenic factors oxidative stress, inflammation, metal toxicity, Aβ accumulation, modulate neurotransmission insulin signaling. review, emphasized neuroprotective effects pathology, both experimental findings. While studies suggest promising benefits, data remains limited inconclusive. Thus, high-quality trials are necessary validate efficacy study aim promote therapies encourage add regular diet avail beneficial preventive

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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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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Oxidative Stress Biomarkers as Preclinical Markers of Mild Cognitive Impairment: The Impact of Age and Sex

Journal of Personalized Medicine, Journal Year: 2025, Volume and Issue: 15(5), P. 171 - 171

Published: April 26, 2025

Background: Reactive oxygen species (ROS) are involved in the pathophysiology of neurodegeneration and cognitive decline, indicating potential use oxidative stress biomarkers for early diagnosis. Mild impairment (MCI) is defined as a decline beyond normal aging, without significant impact on daily functioning, considered an important stage detection neurodegeneration. This study aimed to investigate serum cerebrospinal fluid (CSF) levels biomarkers, total ROS malondialdehyde (MDA) patients with MCI evaluate their utility diagnosis Alzheimer's disease (AD). Levels were also assessed according age sex, well correlation established CSF including amyloid-beta (Aβ40, Aβ42 Aβ42/Aβ40 ratio), phosphorylated tau protein (p-tau) (t-tau). Methods: A 114 adults divided into three groups: (A-) ratio (n = 38), (A+) abnormal 38) healthy function individuals 38). Established conducted using automated immunochemical method, while measured by fluorometry MDA determined competitive inhibition enzyme immunoassay. Results: statistically difference was observed (p < 0.05) between groups. Sex analysis revealed significantly higher males' group 0.05). In terms categorization, markedly older 0.01). Conclusions: These findings highlight importance individualized approaches, investigation profile prevent manage stages MCI, considering demographic factors.

Language: Английский

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