The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases

Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC...

Full description

Saved in:
Bibliographic Details
Main Authors: Rojin Sarallah, Shima Jahani, Alireza Soltani Khaboushan, Amir Kian Moaveni, Maryam Amiri, Masoumeh Majidi Zolbin
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Brain, Behavior, & Immunity - Health
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666354624002102
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832586218693459968
author Rojin Sarallah
Shima Jahani
Alireza Soltani Khaboushan
Amir Kian Moaveni
Maryam Amiri
Masoumeh Majidi Zolbin
author_facet Rojin Sarallah
Shima Jahani
Alireza Soltani Khaboushan
Amir Kian Moaveni
Maryam Amiri
Masoumeh Majidi Zolbin
author_sort Rojin Sarallah
collection DOAJ
description Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies. In AD, dysregulation of this axis contributes to amyloid-β accumulation and tau hyperphosphorylation, leading to synaptic dysfunction and cognitive decline. PD studies reveal that CXCL12/CXCR4 signaling influences dopaminergic neuron survival and microglial activation, affecting cognitive function. In MS, the axis modulates neuroinflammation and demyelination processes, impacting cognitive performance. ALS research indicates that the CXCL12/CXCR4/CXCR7 pathway is involved in motor neuron degeneration and associated cognitive deficits. Across these diseases, the axis influences neuroinflammation, synaptic plasticity, and neuronal survival through various signaling cascades, including PI3K/AKT, MAPK, and JAK/STAT pathways. Emerging evidence suggests that modulating this axis could provide neuroprotective effects and potentially alleviate cognitive symptoms. This review highlights the potential of the CXCL12/CXCR4/CXCR7 axis as a therapeutic target for addressing CI in neurodegenerative diseases. It also underscores the need for further research to fully elucidate its role and develop effective interventions, potentially leading to improved clinical management strategies for these devastating disorders.
format Article
id doaj-art-b1231abe23f94a0db200c029ecb76d68
institution Kabale University
issn 2666-3546
language English
publishDate 2025-02-01
publisher Elsevier
record_format Article
series Brain, Behavior, & Immunity - Health
spelling doaj-art-b1231abe23f94a0db200c029ecb76d682025-01-26T05:05:02ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-02-0143100932The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseasesRojin Sarallah0Shima Jahani1Alireza Soltani Khaboushan2Amir Kian Moaveni3Maryam Amiri4Masoumeh Majidi Zolbin5Islamic Azad University, Tehran, IranMS Research Center Neuroscience Institute, Tehran University of Medical Science, IranPediatric and Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, IranPediatric and Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, IranPediatric and Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, IranPediatric and Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, Iran; Corresponding author. Pediatric Urology and Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, Iran.Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies. In AD, dysregulation of this axis contributes to amyloid-β accumulation and tau hyperphosphorylation, leading to synaptic dysfunction and cognitive decline. PD studies reveal that CXCL12/CXCR4 signaling influences dopaminergic neuron survival and microglial activation, affecting cognitive function. In MS, the axis modulates neuroinflammation and demyelination processes, impacting cognitive performance. ALS research indicates that the CXCL12/CXCR4/CXCR7 pathway is involved in motor neuron degeneration and associated cognitive deficits. Across these diseases, the axis influences neuroinflammation, synaptic plasticity, and neuronal survival through various signaling cascades, including PI3K/AKT, MAPK, and JAK/STAT pathways. Emerging evidence suggests that modulating this axis could provide neuroprotective effects and potentially alleviate cognitive symptoms. This review highlights the potential of the CXCL12/CXCR4/CXCR7 axis as a therapeutic target for addressing CI in neurodegenerative diseases. It also underscores the need for further research to fully elucidate its role and develop effective interventions, potentially leading to improved clinical management strategies for these devastating disorders.http://www.sciencedirect.com/science/article/pii/S2666354624002102CXCL12CXCR4CXCR7Cognitive impairmentNeurodegenerative diseases
spellingShingle Rojin Sarallah
Shima Jahani
Alireza Soltani Khaboushan
Amir Kian Moaveni
Maryam Amiri
Masoumeh Majidi Zolbin
The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases
Brain, Behavior, & Immunity - Health
CXCL12
CXCR4
CXCR7
Cognitive impairment
Neurodegenerative diseases
title The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases
title_full The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases
title_fullStr The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases
title_full_unstemmed The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases
title_short The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases
title_sort role of cxcl12 cxcr4 cxcr7 axis in cognitive impairment associated with neurodegenerative diseases
topic CXCL12
CXCR4
CXCR7
Cognitive impairment
Neurodegenerative diseases
url http://www.sciencedirect.com/science/article/pii/S2666354624002102
work_keys_str_mv AT rojinsarallah theroleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT shimajahani theroleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT alirezasoltanikhaboushan theroleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT amirkianmoaveni theroleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT maryamamiri theroleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT masoumehmajidizolbin theroleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT rojinsarallah roleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT shimajahani roleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT alirezasoltanikhaboushan roleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT amirkianmoaveni roleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT maryamamiri roleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases
AT masoumehmajidizolbin roleofcxcl12cxcr4cxcr7axisincognitiveimpairmentassociatedwithneurodegenerativediseases