Matrix metalloproteinases in peripheral blood and cerebrospinal fluid in patients with Alzheimer's disease

Horstmann, Solveig; Budig, Leila; Gardner, Humphrey; Koziol, James A.; Deuschle, Michael; Schilling, Cláudia; Wagner, Simone

doi:10.1017/s1041610210000827

Cited by 91 publications

(67 citation statements)

References 29 publications

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“…Understanding how MMPs are regulated developmentally during the period of neuronal death may lead to new strategies for preventing neurodegenerative diseases. Genes for MMPs are associated with neurodegenerative diseases (36), and up-regulation of MMPs is reported in patients with Alzheimer disease (37,38) and in animal models of Parkinson disease (39,40). The experimental system we have developed may provide a model to define the molecular mechanism linking ECM signals to survival of neurons in disease.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-9 Regulates Survival of Neurons in Newborn Hippocampus

Murase

McKay

2012

Journal of Biological Chemistry

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Background: Survival of neonatal hippocampal neurons during developmental neuronal death requires integrin. Results: Levels of laminin increase because levels of matrix metalloproteinase-9 decrease during developmental neuronal death. Conclusion: Matrix metalloproteinase-9 regulates survival of neurons by regulating laminin-integrin ␤1 signaling during developmental neuronal death. Significance: This is the first report to show a role of matrix metalloproteinases in the survival mechanism in neurons during a critical developmental process.

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Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-9 Regulates Survival of Neurons in Newborn Hippocampus

Murase

McKay

2012

Journal of Biological Chemistry

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“…MMP-3, for example, has been detected around senile plaques, in the grey matter and in the interstitium between myelinated axons and astrocytes in the white matter of AD patients [387]. MMP-3 is also significantly elevated in the plasma and CSF of AD patients [388]. More recently, the CSF of cognitively-healthy individuals with risk markers for future AD has been found to have higher MMP-3 levels and a higher MMP-3/TIMP-1 ratio than healthy individuals without risk markers [389].…”

Section: C) Alzheimer's Diseasementioning

confidence: 99%

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Gargiulo¹,

Gamba²,

Poli³

et al. 2014

CPD

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Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS).This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

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“…Consistent with these findings, several groups found overexpression of MMP-2, -3, and -9 mRNA and protein in postmortem brains from AD patients. [221][222][223][224] Horstmann et al 225 used zymography and detected MMP-2, -3, -9, and -10 activity levels in serum and CSF from AD patients and compared them to gender-and age-matched healthy control individuals. The authors found that MMP-3 activity was elevated by 40% in plasma and 60% in CSF from AD patients compared to control individuals.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

Rempe

Hartz

Bauer

2016

J Cereb Blood Flow Metab

520

422

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Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood-brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the bloodbrain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer's disease, Parkinson's disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood-brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood-brain barrier in brain disorders.

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Matrix metalloproteinases in peripheral blood and cerebrospinal fluid in patients with Alzheimer's disease

Abstract: These findings constitute further evidence for the important role of MMPs in the pathogenesis of AD.

Cited by 91 publications

References 29 publications

Matrix Metalloproteinase-9 Regulates Survival of Neurons in Newborn Hippocampus

Matrix Metalloproteinase-9 Regulates Survival of Neurons in Newborn Hippocampus

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

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