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Matrix Metalloproteinases and Their Multiple Roles in Alzheimer's Disease
Abstract
Alzheimer’s disease (AD) is the most prevalent type of dementia. Pathological changes in the AD brain include amyloid-β(A β) plaques and neurofibrillary tangles (NFTs), as well as neuronal death and synaptic loss. Matrix metalloproteinases (MMPs) play an important role as inflammatory components in the pathogenesis of AD. MMP-2 might be assumed to have a protective role in AD and is the major MMP which is directly linked to A β in the brain. Synthesis of MMP-9 can be induced by A β, and the enzymes appear to exert multiple effects in AD in senile plaque homoeostasis. The proaggregatory influence on tau oligomer formation in strategic brain regions may be a potential neurotoxic side effect of MMP-9. MMP-3 levels are correlated to the duration of AD and correlate with the CSF T-tau and P-tau levels in the elderly controls. Elevated brain levels of MMP-3 might result in increased MMP-9 activity and indirectly facilitate tau aggregation. At present, the clinical utility of these proteins, particularly in plasma or serum, as potential early diagnostic biomarkers for AD remains to be established. More research is needed to understand the diverse roles of these proteases to design specific drugs and devise therapeutic strategies for AD.
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Elevated levels of MMP14 and aberrant MMP14 activity have been implicated in various age-related neurological conditions associated with cognitive impairment, such as Alzheimer's disease and traumatic brain injury.
“In addition, elevated levels of MMP14 and aberrant MMP14 activity have been implicated in various age-related neurological conditions associated with cognitive impairment, such as Alzheimer’s disease and traumatic brain injury18,19.”
From MT1-MMP inhibition rejuvenates ageing brain and rescues cognitive deficits in obesity (2025) · cites this paper as [18]
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Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Bell, R. D., Winkler, E. A., Singh, I., Sagare, A. P., Deane, R., Wu, Z., Holtzman, D. M., Betsholtz, C., Armulik, A., Sallstrom, J., et al. (2012) · Nature · doi:10.1038/nature11087 · Cited by 1,293 · cited 1×
“Some other studies show that apoE4 significantly dampens Aβ-induced MMP-9 levels, possibly by downregulating the Rho-Rho kinase (ROCK) pathway, and reduction of astrocytic MMP-9 by apoE4 may affect Aβ clearance and promote Aβ deposition in AD [22, 23].”
Propagation of Tau Misfolding from the Outside to the Inside of a Cell
Frost, B., Jacks, R. L., & Diamond, M. I. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808759200 · Cited by 1,252
Matrix Metalloproteinase-9 Degrades Amyloid-β Fibrils in Vitro and Compact Plaques in Situ
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“MMP-9 induces Aβ, degrades Aβ and compact plaques, and is released, along with proNGF, in an activity dependent manner [24].”
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The Infectious Etiology of Alzheimer’s Disease
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Protein-Protein Interactions and Aggregation Inhibitors in Alzheimer’s Disease
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MT1-MMP inhibition rejuvenates ageing brain and rescues cognitive deficits in obesity
Asthana, P., Li, L., Lu, L., Wu, J., Zhang, S., Li, N., Wong, S. K. K., Gurung, S., Zhang, Y., Lin, Y., et al. (2025) · Cell Discovery · doi:10.1038/s41421-025-00825-w · Cited by 4
Kamboj, S., Harms, C., Wright, D., Nash, A., Klein-Seetharaman, J., & Sarkar, S. K. (2022) · doi:10.21203/rs.3.rs-1258797/v1 · Cited by 1
Metadata
- Authors
- Wang, X.-X., Tan, M.-S., Yu, J.-T., & Tan, L.
- Affiliations
- Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao 266071, China
- Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao 266003, China
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2014
- Volume
- 2014
- Pages
- 1-8
- ISSN
- 2314-6133
- 2314-6141
- PMC
- PMC4094696
- Cited by
- 55
- References
- 4
- Language
- en
- Funders
- National Natural Science Foundation of China (81000544, 81171209, 81371406, ZR2010HQ004, ZR2011HZ001)
- Shandong Provincial Natural Science Foundation, China (81000544, 81171209, 81371406, ZR2010HQ004, ZR2011HZ001)
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