Endoplasmic Reticulum Stress Differently Modulates the Release of IL-6 and IL-8 Cytokines in Human Glial Cells DOI Open Access
Paulina Sokołowska, Anna Wiktorowska‐Owczarek, Jakub Tambor

et al.

Published: June 26, 2024

Background: Endoplasmic reticulum (ER) stress is a significant player in the pathophysiology of various neurodegenerative and neuropsychiatric disorders. Despite established link between ER inflammatory pathways, there remains need for deeper exploration specific cellular mechanisms underlying stress-mediated neuroinflammation. Methods: This study aimed to investigate how severity can impact release proinflammatory cyto-kines IL-6 IL-8 from astrocytes microglia, comparing effects with those induced by well-known immunostimulants - tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS). Results: Mild has distinct effect on cytokine compared more intense levels, i.e. diminished production was accompanied an increase level, which significantly pronounced than microglia. On contrary, prolonged severe inflammation glial cells, leading time- concentration-dependent buildup pro-inflammatory but unlike agents, inducer secretions cells. Conclusion: The differences could hold importance identifying markers as potential drug targets treatment diseases mood disorders, yet it requires confirmation complex animal studies.

Language: Английский

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer DOI Creative Commons
S. C. Yuan,

Dan She,

Shangming Jiang

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: March 20, 2024

Abstract The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads stress (ER stress). As ER ensues, protein response (UPR), comprising three signaling pathways—inositol-requiring enzyme 1, kinase R-like kinase, activating transcription factor 6 promptly activates enhance ER’s protein-folding capacity restore homeostasis. However, prolonged levels propels UPR towards cellular demise subsequent inflammatory cascade, contributing development human diseases, including cancer, neurodegenerative disorders, diabetes. Notably, increased expression all pathways has been observed in these pathologies, reduction molecule correlates with decreased proliferation disease-associated target cells. Consequently, therapeutic strategies targeting stress-related interventions have attracted significant research interest. In this review, we elucidate critical role metabolic, offering novel approaches for conditions.

Language: Английский

Citations

40
Melatonin Can Modulate Neurodegenerative Diseases by Regulating Endoplasmic Reticulum Stress DOI Open Access
Yeong‐Min Yoo, Seong Soo Joo

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2381 - 2381

Published: Jan. 25, 2023

As people age, their risks of developing degenerative diseases such as cancer, diabetes, Parkinson’s Disease (PD), Alzheimer’s (AD), rheumatoid arthritis, and osteoporosis are generally increasing. Millions worldwide suffer from these they age. In most countries, neurodegenerative recognized the number one cause afflicting elderly. Endoplasmic reticulum (ER) stress has been suggested to be associated with some human neurological diseases, PD AD. Melatonin, a neuroendocrine hormone mainly synthesized in pineal gland, is involved pleiotropically biological functions, including control circadian rhythm, immune enhancement, antioxidant, anti-aging, anti-tumor effects. Although there many papers on prevention or suppression by melatonin, very few about effects melatonin ER neurons diseases. This paper aims summarize present reported so far, focusing its related stress. Studies have shown that primary target molecule for CHOP, PERK GRP78/BiP secondary molecules. Therefore, crucial protecting treating neurodegeneration against

Language: Английский

Citations

24
Proteostasis disruption and senescence in Alzheimer’s disease pathways to neurodegeneration DOI
Riya Thapa, Asif Ahmad Bhat, Moyad Shahwan

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1845, P. 149202 - 149202

Published: Aug. 30, 2024

Language: Английский

Citations

9
Intranasal Administration of GRP78 Protein (HSPA5) Confers Neuroprotection in a Lactacystin-Induced Rat Model of Parkinson’s Disease DOI Open Access
М. Б. Пази, Д. В. Белан, Elena Y. Komarova

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3951 - 3951

Published: April 2, 2024

The accumulation of misfolded and aggregated α-synuclein can trigger endoplasmic reticulum (ER) stress the unfolded protein response (UPR), leading to apoptotic cell death in patients with Parkinson’s disease (PD). As major ER chaperone, glucose-regulated 78 (GRP78/BiP/HSPA5) plays a key role UPR regulation. GRP78 overexpression modulate UPR, block apoptosis, promote survival nigral dopamine neurons rat model pathology. Here, we explore therapeutic potential intranasal exogenous for preventing or slowing PD-like neurodegeneration lactacystin-induced model. We show that intranasally-administered rapidly enters substantia nigra pars compacta (SNpc) other afflicted brain regions. It is then internalized by microglia, development neurodegenerative process nigrostriatal system. Lactacystin-induced disturbances, such as abnormal phosphorylated pS129-α-synuclein activation pro-apoptotic GRP78/PERK/eIF2α/CHOP/caspase-3,9 signaling pathway are substantially reversed upon administration. Moreover, inhibits both microglia production proinflammatory cytokines, tumor necrosis factor-α (TNF-α) interleukin-6 (IL-6), via nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) animals. neuroprotective anti-inflammatory may inform effective agents PD synucleinopathies.

Language: Английский

Citations

8
Eu(OH)3 and Eu(OH)3-based nanostructures: Synthesis, properties, and uses DOI
Shaidatul Najihah Matussin, Mohammad Hilni Harunsani, Mohammad Mansoob Khan

et al.

Materials Today Communications, Journal Year: 2024, Volume and Issue: 39, P. 108775 - 108775

Published: March 29, 2024

Language: Английский

Citations

7
Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability DOI Creative Commons
Wen Xie, Sushruta Koppula, Mayur B. Kale

et al.

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

Published: Sept. 5, 2024

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible energy production and calcium regulation. This review offers an in-depth examination of interplay between epilepsy, mitochondrial function, aging. Many factors might account correlation epilepsy Mitochondria, integral to dynamics neuronal excitability, perform critical role in pathophysiology epilepsy. The mechanisms linking mitochondria are multifaceted, involving dysfunction, reactive oxygen species (ROS), dynamics. Mitochondrial dysfunction can trigger seizures compromising ATP production, increasing glutamate release, altering ion channel function. ROS, natural byproducts respiration, contribute oxidative stress neuroinflammation, epileptogenesis. govern fusion fission processes, influence seizure threshold buffering, impact propagation. Energy demands during highlight generation maintaining membrane potential. handling dynamically modulates affecting synaptic transmission action potential generation. Dysregulated hallmark contributing excitotoxicity. Epigenetic modifications function through histone modifications, DNA methylation, non-coding RNA expression. Potential therapeutic avenues targeting include mitochondria-targeted antioxidants, ketogenic diets, metabolic therapies. concludes outlining future directions research, emphasizing integrative approaches, advancements ethical considerations. Mitochondria emerge as central players narrative offering profound insights this challenging disorder.

Language: Английский

Citations

5
ER‐phagy in neurodegeneration DOI Creative Commons
Melissa A. Hill, Alex M. Sykes, George D. Mellick

et al.

Journal of Neuroscience Research, Journal Year: 2023, Volume and Issue: 101(10), P. 1611 - 1623

Published: June 19, 2023

Abstract There are many cellular mechanisms implicated in the initiation and progression of neurodegenerative disorders. However, age accumulation unwanted products a common theme underlying diseases including Alzheimer's disease, Parkinson's Niemann–Pick type C. Autophagy has been studied extensively these various genetic risk factors have disruption autophagy homoeostasis as major pathogenic mechanism. is essential maintenance neuronal homeostasis, their postmitotic nature makes them particularly susceptible to damage caused by defective or misfolded proteins, disease‐prone aggregates, damaged organelles. Recently, endoplasmic reticulum (ER‐phagy) identified novel mechanism for regulating ER morphology response stress. As generally precipitated stressors such protein environmental toxin exposure role ER‐phagy begun be investigated. In this review we discuss current research its involvement diseases.

Language: Английский

Citations

13
Strategies targeting endoplasmic reticulum stress to improve Parkinson’s disease DOI Creative Commons
Danni Wang,

Shuhui Qu,

Zaijun Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 10, 2023

Parkinson’s disease (PD) is a common neurodegenerative disorder with motor symptoms, which caused by the progressive death of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc). Accumulating evidence shows that endoplasmic reticulum (ER) stress occurring SNpc DA an early event development PD. ER triggers activation unfolded protein response (UPR) to reduce and restore function. However, excessive continuous UPR exacerbate risk neuron through crosstalk other PD events. Thus, considered promising therapeutic target for treatment Various strategies targeting modulation signaling, increase ER’s folding ability, enhancement degradation are developed alleviate neuronal models. In this review, we summarize pathological role update improve homeostasis PD-related

Language: Английский

Citations

13
Endoplasmic Reticulum Stress Differently Modulates the Release of IL-6 and IL-8 Cytokines in Human Glial Cells DOI Open Access
Paulina Sokołowska, Anna Wiktorowska‐Owczarek, Jakub Tambor

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8687 - 8687

Published: Aug. 9, 2024

Endoplasmic reticulum (ER) stress is a significant player in the pathophysiology of various neurodegenerative and neuropsychiatric disorders. Despite established link between ER inflammatory pathways, there remains need for deeper exploration specific cellular mechanisms underlying stress-mediated neuroinflammation. This study aimed to investigate how severity (triggered by different concentrations tunicamycin) can impact release proinflammatory cytokines IL-6 IL-8 from astrocytes microglia, comparing effects with those induced well-known immunostimulants—tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS). Mild has distinct effect on cytokine compared more intense levels, i.e., diminished production was accompanied an increase level, which significantly pronounced than microglia. On contrary, prolonged severe inflammation glial cells, leading time- concentration-dependent buildup IL-6, but unlike agents, inducer secretions cells. The differences could hold importance identifying markers as potential drug targets treatment diseases mood disorders, yet this requires confirmation complex animal studies.

Language: Английский

Citations

4
A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development DOI Open Access

Jingyun Wu,

Luisa Möhle, Thomas Brüning

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14763 - 14763

Published: Nov. 25, 2022

Huntington's disease (HD) is a lethal neurodegenerative disorder without efficient therapeutic options. The inefficient translation from preclinical and clinical research into use mainly attributed to the lack of (i) understanding initiation, progression, involved molecular mechanisms; (ii) knowledge possible HD target space general data awareness; (iii) detailed characterizations available models; (iv) better suitable (v) reliable sensitive biomarkers. To generate robust HD-like symptoms in mouse model, neomycin resistance cassette was excised zQ175 mice, generating new line: zQ175Δneo. We entirely describe dynamics behavioral, neuropathological, immunohistological changes 15-57 weeks age. Specifically, zQ175Δneo mice showed early astrogliosis 15 weeks; growth retardation, body weight loss, anxiety-like behaviors 29 motor deficits reduced muscular strength 36 finally slight microgliosis at 57 Additionally, we collected entire bioactivity network small-molecule modulators multitarget dataset (HD_MDS). Hereby, uncovered 358 unique compounds addressing over 80 different pharmacological targets pathways. Our will support future drug discovery approaches may serve as useful assessment platform for development against HD.

Language: Английский

Citations

18