Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins
Acute ischemic stroke (AIS) is a focal neurological deficit due to sudden occlusion of cerebral vessels in the brain. AIS-induced neuronal injury and associated excite-toxicity and neurodegeneration affect the synthesis and the release of different neurotrophic factors such as brain-derived neurotro...
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Elsevier
2025-06-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025001509 |
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| author | Hala Alnoaman Hayder M. Al-Kuraishy Ali I. Al-Gareeb Areej Turkistani Albatoul Allam Athanasios Alexiou Marios Papadakis Gaber El-Saber Batiha |
| author_facet | Hala Alnoaman Hayder M. Al-Kuraishy Ali I. Al-Gareeb Areej Turkistani Albatoul Allam Athanasios Alexiou Marios Papadakis Gaber El-Saber Batiha |
| author_sort | Hala Alnoaman |
| collection | DOAJ |
| description | Acute ischemic stroke (AIS) is a focal neurological deficit due to sudden occlusion of cerebral vessels in the brain. AIS-induced neuronal injury and associated excite-toxicity and neurodegeneration affect the synthesis and the release of different neurotrophic factors such as brain-derived neurotropic factor (BDNF) and its precursor proBDNF. Both BDNF and proBDNF act on the specific receptors with different neurological effects. BDNF activates tropomyosin receptor kinase B (TrkB) receptor results in promoting neuronal survival, synaptic plasticity, and neuronal growth. However, the proBDNF activates p75 neurotrophin receptor (p75NTR) and sortilin which attenuates synaptic plasticity and promotes neuronal apoptosis. Dysregulation of central and peripheral expression of proBDNF/BDNF is linked with the severity and clinical outcomes of AIS. Therefore, this review aims to discuss the alterations of proBDNF/BDNF signaling in AIS. Findings from the present review illustrated that proBDNF/p75NTR/sortilin signaling pathway is exaggerated whereas; BDNF-TrkB signaling is reduced in AIS leading to neuronal apoptosis. Therefore, activation of BDNF-TrkB signaling, and inhibition of proBDNF/p75NTR/sortilin signaling pathway could be a promising therapeutic strategy in the management of AIS. |
| format | Article |
| id | doaj-art-eb0efa55edfa44cf95f77934dfa350ec |
| institution | DOAJ |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-eb0efa55edfa44cf95f77934dfa350ec2025-08-20T03:13:39ZengElsevierBrain Research Bulletin1873-27472025-06-0122611133810.1016/j.brainresbull.2025.111338Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same CoinsHala Alnoaman0Hayder M. Al-Kuraishy1Ali I. Al-Gareeb2Areej Turkistani3Albatoul Allam4Athanasios Alexiou5Marios Papadakis6Gaber El-Saber Batiha7Consultant family medicine, Ministry of health, Kingdom of Saudi ArabiaDepartment of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad 14132, IraqHead of Jabir Ibn, Hayyan Medical University, Al-Ameer Qu./Najaf-Iraq, Kufa PO.Box13, Iraq,Department of pharmacology and toxicology, Collage of Medicine, Taif University,Taif 21944, Kingdom of Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), AL-Azhar University, Cairo, Egypt; Corresponding authors.University Centre for Research & Development, Chandigarh University, Mohali, India; Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, New South Wales, Australia; Department of Research & Development, Funogen, Athens, Greece; Department of Research & Development, AFNP Med, Wien, AustriaDepartment of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, Wuppertal, 42283, Germany; Corresponding authors.Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt; Corresponding authors.Acute ischemic stroke (AIS) is a focal neurological deficit due to sudden occlusion of cerebral vessels in the brain. AIS-induced neuronal injury and associated excite-toxicity and neurodegeneration affect the synthesis and the release of different neurotrophic factors such as brain-derived neurotropic factor (BDNF) and its precursor proBDNF. Both BDNF and proBDNF act on the specific receptors with different neurological effects. BDNF activates tropomyosin receptor kinase B (TrkB) receptor results in promoting neuronal survival, synaptic plasticity, and neuronal growth. However, the proBDNF activates p75 neurotrophin receptor (p75NTR) and sortilin which attenuates synaptic plasticity and promotes neuronal apoptosis. Dysregulation of central and peripheral expression of proBDNF/BDNF is linked with the severity and clinical outcomes of AIS. Therefore, this review aims to discuss the alterations of proBDNF/BDNF signaling in AIS. Findings from the present review illustrated that proBDNF/p75NTR/sortilin signaling pathway is exaggerated whereas; BDNF-TrkB signaling is reduced in AIS leading to neuronal apoptosis. Therefore, activation of BDNF-TrkB signaling, and inhibition of proBDNF/p75NTR/sortilin signaling pathway could be a promising therapeutic strategy in the management of AIS.http://www.sciencedirect.com/science/article/pii/S0361923025001509Acute ischemic strokeProBDNFBDNFBDNF-TrkB signaling |
| spellingShingle | Hala Alnoaman Hayder M. Al-Kuraishy Ali I. Al-Gareeb Areej Turkistani Albatoul Allam Athanasios Alexiou Marios Papadakis Gaber El-Saber Batiha Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins Brain Research Bulletin Acute ischemic stroke ProBDNF BDNF BDNF-TrkB signaling |
| title | Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins |
| title_full | Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins |
| title_fullStr | Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins |
| title_full_unstemmed | Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins |
| title_short | Dysregulation of proBDNF/p75NTR and BDNF/TrkB Signaling in Acute Ischemic Stroke: Different Sides of the Same Coins |
| title_sort | dysregulation of probdnf p75ntr and bdnf trkb signaling in acute ischemic stroke different sides of the same coins |
| topic | Acute ischemic stroke ProBDNF BDNF BDNF-TrkB signaling |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025001509 |
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