ArticleNeurobiology of disease2021
A new role for matrix metalloproteinase-3 in the NGF metabolic pathway: Proteolysis of mature NGF and sex-specific differences in the continuum of Alzheimer's pathology.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Determinants of extraction efficiency in human amniotic membrane processing: biological, mechanical, and biochemical factors shaping growth factor yield.Cell and tissue banking · 2026Review
- Associations between cerebrospinal fluid biomarkers related to endothelial dysfunction and Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- Article
- Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Link Between Matrix Metalloproteinases and Alzheimer's Disease Pathophysiology.Molecular neurobiology · 2025Review
- Article
- Modeling late-onset Alzheimer's disease neuropathology via direct neuronal reprogramming.Science (New York, N.Y.) · 2024Article
- Sex-specific associations of matrix metalloproteinases in Alzheimer's disease.Biology of sex differences · 2023Article
- Distinct conformational changes occur within the intrinsically unstructured pro-domain of pro-Nerve Growth Factor in the presence of ATP and MgProtein science : a publication of the Protein Society · 2023Article
- The Role of Extracellular Matrix in Human Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases.Journal of personalized medicine · 2022Review
- The Role of Extracellular Matrix Components in the Spreading of Pathological Protein Aggregates.Frontiers in cellular neuroscience · 2022Review
- Role of Nutritional Support under Clinical Nursing Path on the Efficacy, Quality of Life, and Nutritional Status of Elderly Patients with Alzheimer's Disease.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Alzheimer's Disease: An Update and Insights Into Pathophysiology.Frontiers in aging neuroscience · 2022Review
- The Nerve Growth Factor Metabolic Pathway Dysregulation as Cause of Alzheimer's Cholinergic Atrophy.Cells · 2021Review
- Review
- Nerve growth factor (NGF) pathway biomarkers in Down syndrome prior to and after the onset of clinical Alzheimer's disease: A paired CSF and plasma study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Nerve Growth Factor Compromise in Down Syndrome.Frontiers in aging neuroscience · 2021Review
- Impact ofMediators of inflammation · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Matrix metalloproteinase-3 (MMP-3) has been associated with risk of Alzheimer's disease (AD). In this study we introduce a novel role for MMP-3 in degrading nerve growth factor (NGF) in vivo and examine its mRNA and protein expression across the continuum of AD pathology. We provide evidence that MMP-3 participates in the degradation of mature NGF in vitro and in vivo and that it is secreted from the rat cerebral cortex in an activity-dependent manner. We show that cortical MMP-3 is upregulated in the McGill-R-Thy1-APP transgenic rat model of AD-like amyloidosis. A similar upregulation was found in AD and MCI brains as well as in cognitively normal individuals with elevated amyloid deposition. We also observed that frontal cortex MMP-3 protein levels are higher in males. MMP-3 protein correlated with more AD neuropathology, markers of NGF metabolism, and lower cognitive scores in males but not in females. These results suggest that MMP-3 upregulation in AD might contribute to NGF dysmetabolism, and therefore to cholinergic atrophy and cognitive deficits, in a sex-specific manner. MMP-3 should be further investigated as a biomarker candidate or as a therapeutic target in AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.