Bone Marrow‐Derived GCA<sup>+</sup> Immune Cells Drive Alzheimer's Disease Progression

Zhou, Rui; Wang, Liwen; Chen, Linyun; Feng, Xu; Zhou, Ruoyu; Xiang, Peng; Wen, Jie; Huang, Yan; Zhou, Haiyan

doi:10.1002/advs.202303402

Cited by 3 publications

(2 citation statements)

References 67 publications

(72 reference statements)

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“…Moreover, GCA+ immune cells derived from bone marrow were shown to migrate to the mouse brain through the CCR10-CCL28 axis. This pathway seems to be critical for the progression of Alzheimer's disease [403]. Importantly, CCR10 levels are reduced in hippocampal neurons during pilocarpine-induced status epilepticus in mice [365].…”

Section: Ccr10-ligands and Pharmacological Modulationmentioning

confidence: 98%

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

Ciechanowska,

Mika

2024

IJMS

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Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal–glial–immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.

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Section: Ccr10-ligands and Pharmacological Modulationmentioning

confidence: 98%

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

Ciechanowska,

Mika

2024

IJMS

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“…These EVs are armed with regenerative cargo, growth factors, antiinflammatory cytokines, and neurotrophic molecules, that endorse neuronal survival and plasticity [46,47]. The dichotomy in the role of bone marrow immune cellderived EVs is stark; while some subsets foster neuroprotection and repair, others may convey pro-inflammatory signals, exacerbating neurodegenerative processes [48,49].…”

Section: Deciphering the Influence Of Bone-derived Evs On Neurodegene...mentioning

confidence: 99%

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Liu,

Shen,

Wan

et al. 2024

J Nanobiotechnol

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Neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies.Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: “neurodegenerative disease” OR “Alzheimer’s disease” OR “Parkinson’s disease” OR “Amyotrophic lateral sclerosis” AND “extracellular vesicles” OR “exosomes” OR “outer membrane vesicles” AND “drug delivery systems” AND “blood-brain barrier”. MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.

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Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Liu,

Xiong

et al. 2024

Alzheimer's & Dementia

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Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD. We review the effects of AD on bone from the aspects of AD pathogenic proteins, AD risk genes, neurohormones, neuropeptides, neurotransmitters, brain‐derived extracellular vesicles (EVs), and the autonomic nervous system. Correspondingly, we elucidate the underlying mechanisms of the involvement of bone in the pathogenesis of AD, including bone‐derived hormones, bone marrow‐derived cells, bone‐derived EVs, and inflammation. On the basis of the crosstalk between bone and the brain, we propose potential strategies for the management of AD with the hope of offering novel perspectives on its prevention and treatment.Highlights The pathogenesis of AD, along with its consequent changes in the brain, may involve disturbing bone homeostasis. Degenerative bone disorders may influence the progression of AD through a series of pathophysiological mechanisms. Therefore, relevant bone intervention strategies may be beneficial for the comprehensive management of AD.

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Bone Marrow‐Derived GCA⁺ Immune Cells Drive Alzheimer's Disease Progression

Cited by 3 publications

References 67 publications

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

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Bone Marrow‐Derived GCA+ Immune Cells Drive Alzheimer's Disease Progression

Cited by 3 publications

References 67 publications

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

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Bone Marrow‐Derived GCA⁺ Immune Cells Drive Alzheimer's Disease Progression