Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage
Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, characterized by progressive nerve damage driven by chronic hyperglycemia and systemic inflammation. The pathophysiology of DPN is significantly influenced by pro-inflammatory cytokines, such as IL-1β, IL-6, an...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/3/589 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850203769360351232 |
|---|---|
| author | Zahra Nashtahosseini Majid Eslami Elham Paraandavaji Alireza Haraj Bahram Fadaee Dowlat Ehsan Hosseinzadeh Valentyn Oksenych Ramtin Naderian |
| author_facet | Zahra Nashtahosseini Majid Eslami Elham Paraandavaji Alireza Haraj Bahram Fadaee Dowlat Ehsan Hosseinzadeh Valentyn Oksenych Ramtin Naderian |
| author_sort | Zahra Nashtahosseini |
| collection | DOAJ |
| description | Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, characterized by progressive nerve damage driven by chronic hyperglycemia and systemic inflammation. The pathophysiology of DPN is significantly influenced by pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. These cytokines promote oxidative stress, vascular dysfunction, and neuronal degeneration by activating important signaling pathways including NF-κB and MAPK. While IL-6 promotes a pro-inflammatory microenvironment, increasing neuronal damage and neuropathic pain, TNF-α and IL-1β worsen Schwann cell failure by compromising axonal support and causing demyelination. Immune cell infiltration and TLR activation increase the inflammatory cascade in DPN, resulting in a persistent neuroinflammatory state that sustains peripheral nerve injury. The main characteristics of DPN are axonal degeneration, decreased neurotrophic support, and Schwann cell dysfunction, which weaken nerve transmission and increase susceptibility to damage. Advanced glycation end-products, TNF-α, and CXCL10 are examples of biomarkers that may be used for early diagnosis and disease progression monitoring. Additionally, crucial molecular targets have been found using proteomic and transcriptome techniques, enabling precision medicine for the treatment of DPN. This review emphasizes the importance of cytokine signaling in the pathogenesis of DPN and how cytokine-targeted treatments might reduce inflammation, restore nerve function, and improve clinical outcomes for diabetic patients. |
| format | Article |
| id | doaj-art-e50f2134322a49cd9921725cd0ff439a |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-e50f2134322a49cd9921725cd0ff439a2025-08-20T02:11:25ZengMDPI AGBiomedicines2227-90592025-02-0113358910.3390/biomedicines13030589Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve DamageZahra Nashtahosseini0Majid Eslami1Elham Paraandavaji2Alireza Haraj3Bahram Fadaee Dowlat4Ehsan Hosseinzadeh5Valentyn Oksenych6Ramtin Naderian7Department of Biology, University of Guilan, Rasht 41996-13776, IranCancer Research Center, Semnan University of Medical Sciences, Semnan 35147-99442, IranClinical Research Development Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran 13399-73111, IranStudent Research Committee, Faculty of Medicine, Iran University of Medical Sciences, Tehran 14496-1453, IranFaculty of Medicine, Iran University of Medical Sciences, Tehran 14496-1453, IranDepartment of Surgery, School of Medicine, Semnan University of Medical Sciences, Semnan 35147-99442, IranFaculty of Medicine, University of Bergen, 5020 Bergen, NorwayClinical Research Development Unit, Kowsar Educational, Research and Therapeutic Hospital, Semnan University of Medical Sciences, Semnan 35147-99442, IranDiabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, characterized by progressive nerve damage driven by chronic hyperglycemia and systemic inflammation. The pathophysiology of DPN is significantly influenced by pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. These cytokines promote oxidative stress, vascular dysfunction, and neuronal degeneration by activating important signaling pathways including NF-κB and MAPK. While IL-6 promotes a pro-inflammatory microenvironment, increasing neuronal damage and neuropathic pain, TNF-α and IL-1β worsen Schwann cell failure by compromising axonal support and causing demyelination. Immune cell infiltration and TLR activation increase the inflammatory cascade in DPN, resulting in a persistent neuroinflammatory state that sustains peripheral nerve injury. The main characteristics of DPN are axonal degeneration, decreased neurotrophic support, and Schwann cell dysfunction, which weaken nerve transmission and increase susceptibility to damage. Advanced glycation end-products, TNF-α, and CXCL10 are examples of biomarkers that may be used for early diagnosis and disease progression monitoring. Additionally, crucial molecular targets have been found using proteomic and transcriptome techniques, enabling precision medicine for the treatment of DPN. This review emphasizes the importance of cytokine signaling in the pathogenesis of DPN and how cytokine-targeted treatments might reduce inflammation, restore nerve function, and improve clinical outcomes for diabetic patients.https://www.mdpi.com/2227-9059/13/3/589cytokine signalingdiabetic peripheral neuropathy (DPN)peripheral nerve damageinflammationbiomarker |
| spellingShingle | Zahra Nashtahosseini Majid Eslami Elham Paraandavaji Alireza Haraj Bahram Fadaee Dowlat Ehsan Hosseinzadeh Valentyn Oksenych Ramtin Naderian Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage Biomedicines cytokine signaling diabetic peripheral neuropathy (DPN) peripheral nerve damage inflammation biomarker |
| title | Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage |
| title_full | Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage |
| title_fullStr | Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage |
| title_full_unstemmed | Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage |
| title_short | Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage |
| title_sort | cytokine signaling in diabetic neuropathy a key player in peripheral nerve damage |
| topic | cytokine signaling diabetic peripheral neuropathy (DPN) peripheral nerve damage inflammation biomarker |
| url | https://www.mdpi.com/2227-9059/13/3/589 |
| work_keys_str_mv | AT zahranashtahosseini cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage AT majideslami cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage AT elhamparaandavaji cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage AT alirezaharaj cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage AT bahramfadaeedowlat cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage AT ehsanhosseinzadeh cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage AT valentynoksenych cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage AT ramtinnaderian cytokinesignalingindiabeticneuropathyakeyplayerinperipheralnervedamage |