Cathepsin B Promotes Aβ Proteotoxicity by Modulating Aging Regulating Mechanisms DOI Creative Commons
Ehud Cohen,

Atif Ahmed Siddiqui,

Emmanuelle Merquiol

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 15, 2023

Abstract While the activities of certain proteases promote proteostasis and prevent neurodegeneration-associated phenotypes, protease cathepsin B (CTSB) enhances proteotoxicity in Alzheimer’s disease (AD) model mice, its levels are elevated brains AD patients. How CTSB exacerbates toxicity AD-causing Amyloid β (Aβ), is controversial. Using an activity-based probe, aging-altering interventions nematode C. elegans we discovered that CPR-6 promotes Aβ but mitigates polyQ stretches. knockdown cpr-6 does not affect lifespan, it alleviates by reducing expression swsn-3 elevating level protein SMK-1, both involved regulation aging. These observations unveil a novel mechanism which aggravates Aβ–mediated toxicity, indicate plays opposing roles face distinct proteotoxic insults highlight importance tailoring specific remedies for neurodegenerative disorders.

Language: Английский

Melatonin: Facts, Extrapolations and Clinical Trials DOI Creative Commons
Jean A. Boutin, David J. Kennaway, Ralf Jockers

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(6), P. 943 - 943

Published: June 5, 2023

Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, focus changed from investigating natural role as transducer biological time for physiological systems to hypothesized roles virtually all clinical conditions. This goes along with appearance extensive literature claiming (generally) positive benefits high doses melatonin animal models and various situations would not be receptor-mediated. Based on assumption safe, have been administered patients, including elderly children, trials. this review, we critically review corresponding literature, hypotheses acts scavenger molecule, particular mitochondria, by trying only contextualize these interests but also attempting separate wheat chaff (or wishful thinking facts). We conclude most claims remain experimental evidence used promote them limited sometimes flawed. Our will hopefully encourage researchers reflect what can cannot do help move field forward solid basis.

Language: Английский

Citations

37
Targeting the NRF2 pathway for disease modification in neurodegenerative diseases: mechanisms and therapeutic implications DOI Creative Commons

Clara Mayer,

Lluís Riera‐Ponsati, Sakari Kauppinen

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 25, 2024

Neurodegenerative diseases constitute a global health issue and major economic burden. They significantly impair both cognitive motor functions, their prevalence is expected to rise due ageing societies continuous population growth. Conventional therapies provide symptomatic relief, nevertheless, disease-modifying treatments that reduce or halt neuron death malfunction are still largely unavailable. Amongst the common hallmarks of neurodegenerative protein aggregation, oxidative stress, neuroinflammation mitochondrial dysfunction. Transcription factor nuclear factor-erythroid 2-related 2 (NRF2) constitutes central regulator cellular defense mechanisms, including regulation antioxidant, anti-inflammatory pathways, making it highly attractive therapeutic target for disease modification in disorders. Here, we describe role NRF2 neurodegeneration, review current pharmacological interventions challenges activating pathway, present alternative approaches modification.

Language: Английский

Citations

9
Emodin, a Potent Anthraquinone Mitigates MPTP-Induced Parkinsons’ Disease Pathology by Regulating Nrf2 and Its Downstream Targets: In Silico and In Vivo Approach DOI
Sarwat Jahan, Muhammad Ikram, Sami Siraj

et al.

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

Published: Feb. 20, 2025

Language: Английский

Citations

1
Vitamin D Improves Cognitive Impairment and Alleviates Ferroptosis via the Nrf2 Signaling Pathway in Aging Mice DOI Open Access
Jiaxin Li, Yang Cao, Jie Xu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15315 - 15315

Published: Oct. 18, 2023

Ferroptosis is an iron-dependent mode of cell death associated with the occurrence and development age-related neurodegenerative diseases. Currently, there are no effective drugs available to prevent or treat these aging-related Vitamin D (VD) antioxidant immunomodulator, but its relationship ferroptosis in diseases has not been extensively studied. In this study, we aimed investigate role VD learning memory aging mice. To examine whether protects hippocampal neurons, used physiologically active 1,25(OH)2D3. We established models vivo (C57BL/6 mice) vitro (HT22 cells) using D-galactose (D-gal). The results demonstrated that could improve mice aged via use D-gal, it reduced damage neurons. regulate ferroptosis-related proteins (increasing GPX4 expression decreasing ACSL4 ALOX15 protein levels), increasing GSH levels, reducing MDA intracellular mitochondrial ROS as well total iron Fe2+ improving morphology, thereby alleviating Additionally, activated VDR/Nrf2/HO-1 signaling pathway, inhibiting ferroptosis. Notably, when VDR was knocked down, lost ability activate Nrf2. Consequently, Nrf2 decreased protective effect against summary, activates Nrf2/HO-1 pathway through VDR, effectively preventing induced by

Language: Английский

Citations

21
NOX-induced oxidative stress is a primary trigger of major neurodegenerative disorders DOI Creative Commons
Yuri Zilberter, Dennis R. Tabuena, Misha Zilberter

et al.

Progress in Neurobiology, Journal Year: 2023, Volume and Issue: 231, P. 102539 - 102539

Published: Oct. 12, 2023

Neurodegenerative diseases (NDDs) causing cognitive impairment and dementia are difficult to treat due the lack of understanding primary initiating factors. Meanwhile, major sporadic NDDs share many risk factors exhibit similar pathologies in their early stages, indicating existence common initiation pathways. Glucose hypometabolism associated with oxidative stress is one such primary, shared pathology, a likely cause detrimental disease-associated cascades; targeting this pathology may therefore be an effective preventative strategy for most NDDs. However, its exact trigger remain unclear. Recent research suggests that caused by NADPH oxidase (NOX) activation mechanism among could prove long-sought ubiquitous NDD trigger. We focus on two - Alzheimer's disease (AD) Parkinson's (PD), as well acquired epilepsy which increasingly recognized comorbidity also discuss available data suggesting relevance proposed mechanisms other delve into commonalities these neuroinflammation NOX involvement identify potential therapeutic targets gain deeper underlying causes

Language: Английский

Citations

13
The Role of Nrf2 in the Regulation of Mitochondrial Function and Ferroptosis in Pancreatic Cancer DOI Creative Commons

Dinara Baiskhanova,

H. Schäfer

Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 696 - 696

Published: June 6, 2024

The transcription factor nuclear erythroid 2-related 2 (Nrf2) represents the master regulator of cellular antioxidant response and plays a critical role in tumorigenesis. This includes preventive effect Nrf2 on cell death through ferroptosis, which an essential mechanism therapy resistance malignant tumors, such as pancreatic ductal adenocarcinoma (PDAC) one most aggressive still incurable tumors. Addressing this issue, we provide overview mediated with particular emphasis its mitochondria organelle responsible for execution ferroptosis. We further outline how deregulated adds to progression PDAC, especially respect ferroptosis anti-cancer drug killing is impaired by resistance. Our review discusses recent approaches inhibition natural synthetic compounds overcome based enhanced Finally, outlook therapeutic strategies combined inducing drugs.

Language: Английский

Citations

5
Cys fluorescent probe precisely modified by fluorine revealing oxidative stress mechanism in Parkinson's disease DOI
Yuting Wang,

Huming Yan,

Fangjun Huo

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 57, P. 102401 - 102401

Published: July 13, 2024

Language: Английский

Citations

5
Discovery of the therapeutic potential of naltriben against glutamate-induced neurotoxicity DOI Creative Commons

Hyomin Ahn,

Hyomin Lee, Won‐Seok Choi

et al.

Neurochemistry International, Journal Year: 2025, Volume and Issue: unknown, P. 105928 - 105928

Published: Jan. 1, 2025

Glutamate-induced neuronal death is associated with neurodegeneration including cerebral ischemia. Several μ-opioid receptor antagonists exhibit a neuroprotective activity and have been considered as potential therapeutic option for neurodegenerative disorders. For the first time, our current study unveiled of selective δ-opioid antagonists. A potent, antagonist naltriben, also known potent TRPM7 agonist, displayed prominent protective effect against glutamate-induced toxicity through opioid receptor-independent, TRPM7-independent mechanisms in HT22 cells. Naltriben activated Nrf2 pathway, alleviated Ca

Language: Английский

Citations

0
Molecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature DOI Creative Commons
Sandra Maria Barbalho, Beatriz Leme Boaro,

Jéssica da Silva Camarinha Oliveira

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 133 - 133

Published: Jan. 20, 2025

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by dysregulation molecular pathways and activation brain’s immune system, resulting release pro-inflammatory oxidative molecules. This chronic inflammation exacerbated peripheral leukocyte infiltration into central nervous system. Medicinal plants, with their historical use traditional medicine, have emerged as promising candidates to mitigate neuroinflammation offer sustainable alternative for addressing conditions green healthcare framework. review evaluates effects medicinal plants on neuroinflammation, emphasizing mechanisms action, effective dosages, clinical implications, based systematic search databases such PubMed, SCOPUS, Web Science. The findings highlight that like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, Dioscorea nipponica reduce cytokines (TNF-α, IL-6, IL-1β), inhibit enzymes (COX-2 iNOS), activate antioxidant pathways, particularly Nrf2. NF-κB primary pathway inhibited across studies. While anti-inflammatory potential these significant, variability dosages phytochemical compositions limits translation. Here, we are modulators underscoring therapeutic potential. Future research should focus animal models, standardized protocols, safety assessments, integrating advanced methodologies, genetic studies nanotechnology, enhance applicability disease management.

Language: Английский

Citations

0
Neuropharmacology of endophytic fungal bioactives: Promising leads for brain disorders DOI

Sheetal Vats

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 109 - 132

Published: Jan. 1, 2025

Language: Английский

Citations

0