TY - JOUR
T1 - Analysis of the Relationship between Metalloprotease-9 and Tau Protein in Alzheimer's Disease
AU - Hernandes-Alejandro, Mario
AU - Montaño, Sarita
AU - Harrington, Charles R.
AU - Wischik, Claude M.
AU - Salas-Casas, Andres
AU - Cortes-Reynosa, Pedro
AU - Perez Salazar, Eduardo
AU - Cazares-Apatiga, Javier
AU - Apatiga-Perez, Ricardo
AU - Ontiveros Torres, Miguel Angel
AU - Perry, George
AU - Pacheco-Herrero, Mar
AU - Luna-Muñoz, Jose
N1 - Publisher Copyright:
© 2020 - IOS Press and the authors. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - matrix metalloproteinase-9
KW - molecular dynamics simulation
KW - protein-protein docking
KW - tau protein
UR - http://www.scopus.com/inward/record.url?scp=85088849567&partnerID=8YFLogxK
U2 - 10.3233/JAD-200146
DO - 10.3233/JAD-200146
M3 - Artículo
C2 - 32538846
AN - SCOPUS:85088849567
SN - 1387-2877
VL - 76
SP - 553
EP - 569
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -