Investigation of the role of matrix metalloproteinases in the genetic etiology of Alzheimer's disease

Hoogmartens, Julie; Hens, Elisabeth; Engelborghs, Sebastiaan; Deyn, Peter Paul De; Zee, Julie van der; Broeckhoven, Christine Van; Cacace, Rita

doi:10.1016/j.neurobiolaging.2021.03.011

Cited by 13 publications

(9 citation statements)

References 28 publications

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“…As an important member of the MMP family, MMP-9 is expressed at a low level in the brain tissue and shows an abnormal upward trend in the occurrence of brain injury, AD, and other neurodegenerative diseases. Hoogmartens et al [ 32 ] believed that MMP-9 is highly expressed in patients suffering from cerebral ischemia and brain injury, and patients with a high expression of MMP-9 have a greater proportion of poor prognosis. Similar data were obtained in this study, indicating that MMP-9 can increase the clinical risk of neurodegenerative diseases, and this indicator is an independent risk factor for neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Matrix Metalloproteinases in the Risk of Cardiovascular and Neurodegenerative Diseases

Huang

Xin-yang

Zhu

et al. 2022

BioMed Research International

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Objective. To investigate the risk of cardiovascular and neurodegenerative diseases induced by matrix metalloproteinases (MMPs) by meta-analysis. Methods. Relevant literature was searched from Wanfang Medical Center, CNQI, VIP, PubMed, and other domestic and foreign literature databases for the research direction, and the risk of cardiovascular and neurodegenerative diseases induced by MMPs was meta-analyzed using the fixed-effect model and random-effect model. Results. MMP-1 and MMP-9 were risk factors for cardiovascular diseases by fixed and random-effect model analysis, respectively, while MMP-2 and MMP-9 were risk factors for increased neurodegenerative diseases by random-effect model analysis. Conclusion. MMP-1 and MMP-9 are risk factors for cardiovascular diseases, and MMP-2 and MMP-9 are major factors for increased risk of neurodegenerative diseases. MMP-1, MMP-2, and MMP-9 can be used as new targets for clinical diagnosis, treatment, and research of subsequent cardiovascular and neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Matrix Metalloproteinases in the Risk of Cardiovascular and Neurodegenerative Diseases

Huang

Xin-yang

Zhu

et al. 2022

BioMed Research International

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“…Elevated expression of MMP-2 is associated with A β induced neuronal cell death, a pathological hallmark of AD [ 26 ]. MMP-2 regulates many signaling molecules, including neuro-inflammation, synaptic dysfunction, and neuronal death [ 27 ]. It is known for remodeling the pericellular environment by regulating the cleavage of extracellular matrix proteins, cell surface components, neurotransmitter receptors, and growth factors [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer’s Disease: A Pilot Study

Saiyed,

Yilmaz,

Vishweswariah

et al. 2023

Journal of Alzheimer's Disease Reports

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Background: Alzheimer’s disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest. Objective: This study aimed to identify potential biomarkers for early detection of AD by analyzing urinary cytokine concentrations. We investigated 37 cytokines in AD, MCI, and cognitively normal individuals (NC), assessing their associations with AD development. Methods: Urinary cytokine concentrations were measured in AD (n = 25), MCI (n = 25), and NC (n = 26) patients. IL6ST and MMP-2 levels were compared between AD and NC, while TNFRSF8, IL6ST, and IL-19 were assessed in AD versus MCI. Diagnostic models distinguished AD from NC, and in-silico analysis explored molecular mechanisms related to AD. Results: Significant perturbations in IL6ST and MMP-2 concentrations were observed in AD urine compared to NC, suggesting their potential as biomarkers. TNFRSF8, IL6ST, and IL-19 differed significantly between AD and MCI, implicating them in disease progression. Diagnostic models exhibited promising performance (AUC: 0.59–0.79, sensitivity: 0.72–0.80, specificity: 0.56–0.78) in distinguishing AD from NC. In-silico analysis revealed molecular insights, including relevant non-coding RNAs, microRNAs, and transcription factors. Conclusion: This study establishes significant associations between urinary cytokine concentrations and AD and MCI. IL6ST, MMP-2, TNFRSF8, IL6ST, and IL-19 emerge as potential biomarkers for early detection of AD. In-silico analysis enhances understanding of molecular mechanisms in AD. Further validation and exploration of these biomarkers in larger cohorts are warranted to assess their clinical utility.

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“…Activation of the BMP4-SMAD1/5/9-RUNX2 pathway will inhibit the neurogenesis and oligodendrogenesis of iPSCs in AD patients with age-related diseases [99]. Upregulation of p38MAPK, a well-known SASP regulator, and an increase in SASP factors such as the pro-inflammatory cytokines IL-6, IL-1β, TGF-β, and TNF-α, as well as the extracellular proteases MMP-1, MMP-3, and MMP-10, were observed in AD brains [100][101][102][103][104]. Brain samples were obtained from older adults and AD patients after death, and it was found that AD patients had a significantly higher proportion of senescent astrocytes in the frontal cortex compared to normal age-matched individuals.…”

Section: Neurodegenerative Diseasementioning

confidence: 99%

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies

2024

Aging dis

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Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs) and senomorphics (compounds that alter intercellular communication and modulate the behavior of SnCs) have become hot research topics in the field of anti-aging. In addition, strategies such as combination therapies and immune-based approaches have also made significant progress in the field of antiaging therapy. In this article, we discuss the latest research on anti-aging targeting SnCs and gain a deeper understanding of the mechanism of action and impact of different anti-aging strategies on aging and age-related diseases, with the aim of providing more effective references and therapeutic ideas for clinical anti-aging treatment in the face of the ever-grave challenges of aging and age-related diseases.

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Investigation of the role of matrix metalloproteinases in the genetic etiology of Alzheimer's disease

Cited by 13 publications

References 28 publications

Meta-Analysis of Matrix Metalloproteinases in the Risk of Cardiovascular and Neurodegenerative Diseases

Meta-Analysis of Matrix Metalloproteinases in the Risk of Cardiovascular and Neurodegenerative Diseases

Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer’s Disease: A Pilot Study

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies

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