iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy DOI Open Access
Parveen Parasar,

Navtej Kaur,

Laila Poisson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 10, 2022

SUMMARY X-linked adrenoleukodystrophy (X-ALD) is an inherited progressive metabolic disorder caused by pathogenic variants in the ABCD1 gene, which leads to accumulation of very long chain fatty acids body fluids and tissues including brain spinal cord. In absence a clear genotype-phenotype correlation molecular mechanisms severe cerebral (cALD) milder adrenomyeloneuropathy (AMN) phenotypes remain unknown. Given our previous evidence role astrocytes neuroinflammatory response X-ALD we investigated profiles derived from induced pluripotent stem cells (iPSC). The iPSCs were turn generated skin fibroblasts healthy controls patients with AMN or cALD. cALD exhibited lack acids, hallmark disease. Further, harbor significantly higher phosphorylation STAT3, increased Toll-like receptor expression chemokine cytokine expression. this first report miRNA sequencing astrocytes, observed that miR-9 was associated increasing disease severity phenotype. CRISPR-Cas9 knock-in ABCD1ABCD1 gene differentially affected key molecular, microRNA targets astrocytes. Extensive characterization iPSC-derived astrocyte model demonstrates critical aspects inflammatory mutation can be further utilized for exploring contribution differential

Language: Английский

Differentiation and regulation of CD4+ T cell subsets in Parkinson’s disease DOI Creative Commons
Xiaowei Sun,

Rou Gu,

Jie Bai

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Aug. 17, 2024

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its hallmark pathological features are loss of dopaminergic (DA) neurons in midbrain substantia nigra pars compacta (SNpc) accumulation alpha-synuclein (α-syn). It has been shown that integrity blood-brain barrier (BBB) damaged PD patients, a large number infiltrating T cells inflammatory cytokines have detected cerebrospinal fluid (CSF) brain parenchyma patients animal models, including significant change proportion different CD4

Language: Английский

Citations

3

Dietary Supplementation of Edible Mushroom Phallus atrovolvatus Aqueous Extract Attenuates Brain Changes in the AppNL−G−F Mouse Model of Alzheimer’s Disease DOI Open Access

Raweephorn Kaewsaen,

Wasaporn Chanput,

Lalida Rojanathammanee

et al.

Nutrients, Journal Year: 2025, Volume and Issue: 17(10), P. 1677 - 1677

Published: May 15, 2025

Background/Objectives: Alzheimer's disease (AD) is a neurodegenerative characterized by progressive dementia and brain accumulation of Aβ-peptide-containing plaques, gliosis, neuroimmune changes, neurofibrillary tangles. Mushroom polysaccharides have been previously reported to anti-neuroinflammation activity through the gut-brain axis. This study aimed evaluate whether dietary intervention with Phallus atrovolvatus, recently identified edible mushroom in Thailand, could benefit on gut health alleviate AD-related changes. Methods: Male female 6-8-month-old littermate wild-type control (C57BL/6J) AppNL-G-F mice were randomly assigned either diet or supplemented aqueous extract (MAE) for 8 weeks quantify changes body weight, intestine, immune cells, short chain fatty acids, cytokines, amyloid-β (Aβ) levels, memory. Results: MAE had no adverse effects leakiness increased pyruvate levels serum. Splenocyte profiling revealed significant increase frequency IgM+, IA_IE+, CD14+ cells MAE-administered AppNL-G-Ffemale compared their vehicle controls. AppNL-G-Fmale that received showed cytotoxic CD8 T within cervical lymph nodes counterparts. Aβ deposition gliosis significantly reduced hippocampi MAE-supplemented groups. However, feeding did not alter spatial recognition memory sex genotype Conclusions: Our findings demonstrated administration P. atrovolvatus neuroprotective potential against impact

Language: Английский

Citations

0

A glance through the effects of CD4+ T cells, CD8+ T cells, and cytokines on Alzheimer's disease DOI
Atefeh Afsar, Min Chen, Zhenyu Xuan

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2023, Volume and Issue: 21, P. 5662 - 5675

Published: Jan. 1, 2023

Language: Английский

Citations

7

SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators DOI Creative Commons

Saskia Wedel,

Lisa Hahnefeld,

Yannick Schreiber

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: June 24, 2023

Chemotherapy-induced neuropathic pain (CIPN) describes a pathological state that occurs dose-dependently as side effect and can limit or even impede an effective cancer therapy. Unfortunately, current treatment possibilities for CIPN are remarkably confined mostly inadequate therapeutics themselves consist of low effectiveness may induce severe effects, pointing out entity with emerging need novel targets. Here, we investigated whether the highly specific FKBP51 inhibitor SAFit2 reduces paclitaxel-induced pain.In this study, used well-established multiple low-dose paclitaxel model to investigate analgesic anti-inflammatory properties SAFit2. For purpose, behavior mice was recorded over 14 days mouse tissue then analyzed using biochemical methods.Here, show is capable reduce mechanical hypersensitivity in mice. In addition, detected shifts lipid levels nervous toward pro-resolving profile counteracts peripheral sensitization after treatment. Furthermore, reduced activation astrocytes microglia spinal cord well pain-mediating chemokines. Its also increased cytokines neuronal tissues, ultimately leading resolution neuroinflammation.In summary, shows antihyperalgesic it ameliorates by reducing resolving neuroinflammation. Therefore, consider potential drug candidate pain.

Language: Английский

Citations

6

Increased IL-22 in cerebrospinal fluid of neuro-behçet’s disease patients DOI Creative Commons
Mériam Belghith, Olfa Maghrebi,

Rafika Ben Laamari

et al.

Cytokine, Journal Year: 2024, Volume and Issue: 179, P. 156617 - 156617

Published: April 16, 2024

Remitting-Relapsing Multiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuro-inflammatory disorders leading to brain damage disability in young adults. Herein, we investigated these patients the cytokine response by beads-based multiplex assays during early stages of disorders. Cytokine investigations were carried out on treatment-naive suffering from RRMS NBD recruited at first episode clinical relapse. Our findings demonstrate that Cerebrospinal Fluid (CSF) cells patients, but not RRMS, secrete significant high levels IL-22 which is associated with elevated mRNA expression. We also observed an increase definite subgroup as compared probable one, indicating a clear relationship between diagnostic certainty. Interestingly, found no correlation secretion CSF serum arguing about intrathecal release CNS patients. Moreover, showed correlogram analysis this doesn't correlate IL-17A, IL-17F IL-21 suggesting secreted Th22 Th17 Finally, IL-6 positive IL 6 NBD. In conclusion, results suggest contributes production T exacerbation inflammation within

Language: Английский

Citations

1

Cytokines and Madness: A Unifying Hypothesis of Schizophrenia Involving Interleukin-22 DOI Open Access
Adonis Sfera, Kyle Thomas,

Jacob Anton

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12110 - 12110

Published: Nov. 11, 2024

Schizophrenia is a severe neuropsychiatric illness of uncertain etiopathogenesis in which antipsychotic drugs can attenuate the symptoms, but patients rarely return to premorbid level functioning. In fact, with each relapse, people living schizophrenia progress toward disability and cognitive impairment. Moreover, our desire live normal lives, manage their daily affairs independently, date, get married, raise support family. Those us who work know that these objectives are met despite novel allegedly improved dopamine blockers. We hypothesize poor outcomes reflect gray matter volume reduction, continues treatment. further increased gut barrier permeability, due dysfunctional aryl hydrocarbon receptor (AhR), downregulates protectors, brain-derived neurotrophic factor (BDNF), interleukin-22 (IL-22), facilitating microbial translocation into systemic circulation, eventually reaching brain. Recombinant human IL-22 could ameliorate outcome by limiting bacterial initiating tissue repair. This short review examines signal transducer transcription-three (STAT3)/AhR axis downregulation BDNF subsequent increase permeability. Based on hypothesis presented here, we discuss alternative interventions, including AhR antagonists, mitochondrial transplant, membrane lipid replacement, recombinant IL-22.

Language: Английский

Citations

1

Levels of circulating cytokines in children with multiple sclerosis with different effectiveness of interferon therapy DOI Creative Commons
Т. В. Радыгина, С. В. Петричук,

O. V. Kurbatova

et al.

Allergology and Immunology in Pediatrics, Journal Year: 2024, Volume and Issue: 4, P. 31 - 39

Published: Jan. 8, 2024

Multiple sclerosis (MS) is a chronic, demyelinating disease that leads to disability. Understanding the etiology of MS contributes development pathogenetic methods treatment, and search for informative biomarkers effectiveness treatment will allow patient adjust therapy in time. The aim this work was determine cytokines cytokine profiles predict IFN-β1a children with MS. Materials . 66 aged 16 [14.2–17.5] years who are on INFß-1a were examined: group 1 — patients exacerbation (with active foci demyelination by MRI), n = 34; 2 remission (without foci), 32. content blood serum assessed using multiplex panel Human Th17 Magnetic Bead Panel. Results : There significant increase concentrations compared remission: IL5, IL6, IL9, IL12p70, IL17E/IL25, IL21, IL28A, GM-CSF, TNFß. Threshold values IL9 (AUC 0,785), IL6 0,750), TNFß (0,740), IL28A 0,744) obtained above which it possible an patients: 3.9 pg/ml (Sn 70.6, Sp 71.9), 4.0 68.8), 6.6 243.0 71.9). Cytokine associated T-lymphocytes their functions evaluated z-score. Conclusions For first time, levels demonstrated An proinflammatory Th1 Th17, as well Th2 Th22 has been shown. use threshold TNFβ, help

Language: Английский

Citations

0

The association of maternal COVID-19-infection during pregnancy on the neonatal immune profile and associations with later diagnosis of neurodevelopmental disorders DOI Creative Commons
Danielle Kim, Lisa Croen, Ana‐Maria Iosif

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 123, P. 1071 - 1080

Published: Nov. 10, 2024

Language: Английский

Citations

0

iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy DOI Open Access
Parveen Parasar,

Navtej Kaur,

Laila Poisson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 10, 2022

SUMMARY X-linked adrenoleukodystrophy (X-ALD) is an inherited progressive metabolic disorder caused by pathogenic variants in the ABCD1 gene, which leads to accumulation of very long chain fatty acids body fluids and tissues including brain spinal cord. In absence a clear genotype-phenotype correlation molecular mechanisms severe cerebral (cALD) milder adrenomyeloneuropathy (AMN) phenotypes remain unknown. Given our previous evidence role astrocytes neuroinflammatory response X-ALD we investigated profiles derived from induced pluripotent stem cells (iPSC). The iPSCs were turn generated skin fibroblasts healthy controls patients with AMN or cALD. cALD exhibited lack acids, hallmark disease. Further, harbor significantly higher phosphorylation STAT3, increased Toll-like receptor expression chemokine cytokine expression. this first report miRNA sequencing astrocytes, observed that miR-9 was associated increasing disease severity phenotype. CRISPR-Cas9 knock-in ABCD1ABCD1 gene differentially affected key molecular, microRNA targets astrocytes. Extensive characterization iPSC-derived astrocyte model demonstrates critical aspects inflammatory mutation can be further utilized for exploring contribution differential

Language: Английский

Citations

0