Macrophages protect against sensory axon degeneration in diabetic neuropathy DOI Creative Commons
Clifford J. Woolf, Sara Hakim, Aakanksha Jain

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Abstract Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain1,2. Although the onset progression DPN have been linked with dyslipidemia hyperglycemia3, contribution inflammation in pathogenesis has not investigated. Here, we use High Fat Fructose Diet (HFHFD) to model its metabolic syndrome mice. mice develop persistent heat hypoalgesia after three months, but reduction epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, find that CCR2+ macrophages infiltrate sciatic nerves diabetic well before axonal degeneration detectable. We show these infiltrating share gene expression similarities nerve crush-induced macrophages4 express neurodegeneration-associated microglia marker genes5 although there no axon or demyelination yet. Inhibiting this macrophage recruitment by genetically pharmacologically blocking CCR2 signaling results more severe accelerated denervation. These findings reveal novel neuroprotective into delays terminal degeneration, thereby reducing loss. Potentiating sustaining early immune response patients represents, therefore, potential means reduce prevent DPN.

Language: Английский

Macrophages protect against sensory axon degeneration in diabetic neuropathy DOI Open Access
Sara Hakim, Aakanksha Jain, Veselina Petrova

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 30, 2024

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain

Language: Английский

Citations

5
Association of systemic immune inflammatory index with obesity and abdominal obesity: A cross-sectional study from NHANES DOI

Linjie Qiu,

Yan Ren, Jixin Li

et al.

Nutrition Metabolism and Cardiovascular Diseases, Journal Year: 2024, Volume and Issue: 34(10), P. 2409 - 2419

Published: June 13, 2024

Language: Английский

Citations

4
Macrophages protect against sensory axon loss in peripheral neuropathy DOI Creative Commons
Sara Hakim, Aakanksha Jain, Stuart Adamson

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0
Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress DOI Creative Commons

Chulbul M. Ahmed,

Howard M. Johnson, Alfred S. Lewin

et al.

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

Published: July 22, 2024

Several blinding diseases affecting the retina and optic nerve are exacerbated by or caused dysregulated inflammation oxidative stress. These include uveitis, age related macular degeneration, diabetic retinopathy glaucoma. Consequently, despite their divergent symptoms, treatments that reduce stress suppress may be therapeutic. The production of inflammatory cytokines activities regulated a class proteins termed Suppressors Cytokine Signaling (SOCS). SOCS1 SOCS3 known to dampen signaling via pathways employing Janus kinases signal transducer activator transcription (JAK/STAT), Toll-like Receptors (TLR), nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB), mitogen kinase (MAPK) NLR family pyrin domain containing 3 (NLRP3). We have developed cell-penetrating peptides from inhibitory region (denoted as R9-SOCS1-KIR R9-SOCS3-KIR) tested them in retinal pigment epithelium (RPE) macrophage cell lines. SOCS-KIR exhibited anti-inflammatory, anti-oxidant anti-angiogenic properties. In culture, both Th1 Th17 were suppressed together with inhibition other markers. also observed decrease oxidants simultaneous rise neuroprotective effectors. addition, treatment prevented loss gap junction ensuing drop transepithelial electrical resistance RPE cells. When mouse models eye instillation, they showed protection against autoimmune prophylactic well Mice endotoxin-induced uveitis protected administration well. R9-SOCS3-KIR was particularly effective acting through STAT3, e.g. IL-6 VEGF-A mediated responses lead degeneration. Eye stimulated antioxidant effectors reduced clinical symptoms model replicates injury occurring AMD. Because these multiple pathogenic stimuli because can delivered topically cornea, attractive candidates for therapeutics

Language: Английский

Citations

2
Targeting white adipose tissue to combat insulin resistance DOI

Yiheng Huang,

Pingyi Gao,

Lawrence H. Young

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(10), P. 868 - 871

Published: July 24, 2024

Language: Английский

Citations

2
Macrophages protect against sensory axon degeneration in diabetic neuropathy DOI Creative Commons
Clifford J. Woolf, Sara Hakim, Aakanksha Jain

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Abstract Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, causing sensory loss and debilitating neuropathic pain1,2. Although the onset progression DPN have been linked with dyslipidemia hyperglycemia3, contribution inflammation in pathogenesis has not investigated. Here, we use High Fat Fructose Diet (HFHFD) to model its metabolic syndrome mice. mice develop persistent heat hypoalgesia after three months, but reduction epidermal skin innervation only manifests at 6 months. Using single-cell sequencing, find that CCR2+ macrophages infiltrate sciatic nerves diabetic well before axonal degeneration detectable. We show these infiltrating share gene expression similarities nerve crush-induced macrophages4 express neurodegeneration-associated microglia marker genes5 although there no axon or demyelination yet. Inhibiting this macrophage recruitment by genetically pharmacologically blocking CCR2 signaling results more severe accelerated denervation. These findings reveal novel neuroprotective into delays terminal degeneration, thereby reducing loss. Potentiating sustaining early immune response patients represents, therefore, potential means reduce prevent DPN.

Language: Английский

Citations

0