Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases DOI Creative Commons
Nebojša Brezić,

Strahinja Gligorevic,

Aleksandar Sič

и другие.

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(4), С. 259 - 259

Опубликована: Апрель 8, 2025

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) are characterized progressive neuronal loss cognitive or motor decline, often underpinned pathological protein misfolding aggregation. Emerging evidence suggests potential mechanistic link between chronic NDs, with contributing neuroinflammatory states homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis aggregation serve bridge We systematically examine molecular pathways misfolding, proteostasis dysfunction shared neuroimmune mechanisms, highlighting prion-like propagation misfolded proteins, neuroinflammation, oxidative stress common denominators. further discuss from experimental models clinical studies linking accelerated pathology—including tau accumulation, amyloid dysregulation, microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting aggregation, enhancing chaperone function, modulating unfolded response (UPR), attenuating glial activation explored strategies mitigate possibly slow Understanding this intersection not only elucidates pain’s role decline but also interventions addressing inflammation could yield dual benefits management modification.

Язык: Английский

Indole-3-acetic acid and chenodeoxycholic acid attenuate TLR4/NF-κB signaling and endoplasmic reticulum stress in valproic acid-induced neurotoxicity DOI Creative Commons
Wedad S. Sarawi, Ahlam M. Alhusaini,

Ghada S. Barwaished

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 24, 2025

Valproic acid (VA) is a commonly prescribed medication for epilepsy and other neurological conditions. Although effective, VA use can lead to neurotoxicity, especially with chronic use. This study aimed investigate the potential neuroprotective properties of indole-3-acetic (IAA) chenodeoxycholic (CDCA) in an animal model VA-induced brain injury. Rats received intraperitoneal injections at dose 500 mg/kg/day 3 weeks. Concurrently, they were orally treated IAA (40 mg/kg/day) and/or CDCA (90 mg/kg/day). The results showed significantly increased oxidative stress inflammation markers VA-exposed group indicated by reduced levels glutathione (GSH, P < 0.0001) superoxide dismutase (SOD, 0.01) elevated inflammatory cytokines Interleukin-6 (IL-6, tumor necrosis factor-alpha (TNFα, 0.01). also induced nuclear factor kappa B (NF-κB, 0.01), toll-like receptor 4 (TLR4, 0.05), endoplasmic reticulum (ER) markers, as evidenced immunoreactivity GRP78 (glucose-regulated protein 78, 0.0001), transcription 6 (ATF-6, 0.05) CHOP (C/EBP homologous protein, 0.0001). Treatment or attenuated variable extent, improving oxidative, inflammatory, ER markers. demonstrates that exert protective effects against neurotoxicity mitigating stress, inflammation, stress. Further investigations are recommended validate these findings models.

Язык: Английский

Процитировано

0
Increased Oxidative Stress and Autophagy in NGLY1 Patient iPSC-derived Neural Stem Cells DOI Creative Commons
Zeenat A. Shyr,

Soukaina Amniouel,

Kofi Owusu-Ansah

и другие.

Experimental Cell Research, Год журнала: 2025, Номер unknown, С. 114540 - 114540

Опубликована: Апрель 1, 2025

NGLY1 (N-glycanase) is a de-glycosylating enzyme that promotes clearance of misfolded glycan proteins. deficiency leads to disease pathology with varied symptoms, including severe neurological defects. There are no therapeutic options currently available for the treatment this rare disease. With goal finding potential avenues, we performed comprehensive characterization aberrant cellular stress pathways in patient relevant model deficiency. For more accurate study without other confounding factors, compared differences between iPSC-derived neural stem cells carrying commonly occurring nonsense mutation c.1201A>T (p.R401X) and their genetically similar CRISPR-corrected isogenic controls. Our findings demonstrate an upregulation ER stress, increased autophagic flux significant signs oxidative stress. These results provide new insights into dysfunctions associated disorder. Moreover, they point better establishing reliable high throughput phenotypic assays can be utilized drug discovery.

Язык: Английский

Процитировано

0
Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases DOI Creative Commons
Nebojša Brezić,

Strahinja Gligorevic,

Aleksandar Sič

и другие.

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(4), С. 259 - 259

Опубликована: Апрель 8, 2025

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) are characterized progressive neuronal loss cognitive or motor decline, often underpinned pathological protein misfolding aggregation. Emerging evidence suggests potential mechanistic link between chronic NDs, with contributing neuroinflammatory states homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis aggregation serve bridge We systematically examine molecular pathways misfolding, proteostasis dysfunction shared neuroimmune mechanisms, highlighting prion-like propagation misfolded proteins, neuroinflammation, oxidative stress common denominators. further discuss from experimental models clinical studies linking accelerated pathology—including tau accumulation, amyloid dysregulation, microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting aggregation, enhancing chaperone function, modulating unfolded response (UPR), attenuating glial activation explored strategies mitigate possibly slow Understanding this intersection not only elucidates pain’s role decline but also interventions addressing inflammation could yield dual benefits management modification.

Язык: Английский

Процитировано

0