Analysis of the Relationship Between Metalloprotease-9 and Tau Protein in Alzheimer's Disease

Mario Hernandes-Alejandro* (Corresponding Author), Sarita Montaño, Charles R Harrington, Claude M Wischik, Andrés Salas-Casas, Pedro Cortes-Reynosa, Eduardo Pérez Salazar, Javier Cazares-Apatiga, Ricardo Apatiga-Perez, Miguel Ángel Ontiveros Torres, George Perry, Mar Pacheco-Herrero, José Luna-Muñoz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


BACKGROUND: Neurofibrillary tangles (NFTs) and amyloid plaques are the neuropathological hallmarks in brains with Alzheimer's disease (AD). Post-translational modifications of tau, such as phosphorylation and truncation, have been proposed as initiators in the assembly of the abnormal paired helical filaments that constitute the NFTs. Neurons and NFTs are sites of matrix metalloproteinases (MMPs).

OBJECTIVE: The aim of this study was to analyze the relationship of MMP-9 and tau protein in brain samples with AD.

METHODS: This study was performed on brain tissue samples from patients with early, moderate, and late AD. MMPs and tau levels were analyzed by western blot and gelatin-substrate zymography. Immunofluorescence techniques and confocal microscopy were used to analyze the presence of both proteins in NFTs. Further, molecular dynamics simulations (MDS) and protein-protein docking were conducted to predict interaction between MMP-9 and tau protein.

RESULTS: MMP-9 expression was greatest in moderate and late AD, whereas MMP-2 expression was only increased in late-stage AD. Interestingly, confocal microscopy revealed NFTs in which there was co-localization of MMP-9 and tau protein. MDS and protein-protein docking predictions indicate that a high-affinity complex can be formed between MMP-9 and full-length tau protein.

CONCLUSION: These observations provide preliminary evidence of an interaction between these two proteins. Post-translational modifications of tau protein, such as C-terminal truncation or phosphorylation of amino acid residues in the MMP-9 recognition site and conformational changes in the protein, such as folding of the N-terminal sequence over the three-repeat domain, could preclude the interaction between MMP-9 and tau protein during stages of NFT development.

Original languageEnglish
Pages (from-to)553-569
Number of pages17
JournalJournal of Alzheimer's Disease
Issue number2
Publication statusPublished - 21 Jul 2020


  • Alzheimer’s disease
  • matrix metalloproteinase-9
  • molecular dynamics simulation
  • protein-protein docking
  • tau protein
  • Alzheimer's disease


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