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For instance, it is known that selective and short-term inhibition of MMP-14, a membrane-type 1 MMP, accelerates axon regeneration. Because axon growth and regeneration is impaired in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by misfolding and deposition of mutant transthyretin (TTR) in the peripheral nervous system (PNS), we presently investigated the expression levels and the potential role for MMP-14 in this condition. By using cell culture studies, a mouse model of disease and human clinical samples, we observed that MMP-14: (i) is overexpressed in FAP nerves, correlating with TTR deposition; (ii) is upregulated in sciatic nerves from a preclinical transgenic mouse model, increasing with TTR deposition; (iii) levels in the PNS and plasma are rescued upon treatment of mice with anakinra or TTR siRNA, drugs acting over the IL-1 signaling pathway or TTR liver synthesis, respectively; (iv) increases in Schwann cells upon incubation with amyloid-like aggregates; and, finally, (v) is increased in plasma of FAP patients, correlating with disease progression. These results highlight the relevance of MMP-14 in the pathophysiology of FAP, suggesting not only a potential role for this molecule as a novel biomarker for therapy follow up, but also as a new potential therapeutic target.<\/jats:p>","DOI":"10.1242\/dmm.028571","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T08:50:22Z","timestamp":1507539022000},"page":"1253-1260","source":"Crossref","is-referenced-by-count":27,"title":["MMP-14 overexpression correlates with the neurodegenerative process in familial amyloidotic polyneuropathy"],"prefix":"10.1242","volume":"10","author":[{"given":"Diana","family":"Martins","sequence":"first","affiliation":[{"name":"Instituto de Inova\u00e7\u00e3o e Investiga\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Moreira","sequence":"additional","affiliation":[{"name":"Instituto de Inova\u00e7\u00e3o e Investiga\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Neurobiologia Molecular - Instituto de Biologia Molecular (IBMC), Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00e1dia Pereira","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Instituto de Inova\u00e7\u00e3o e Investiga\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Neurobiologia Molecular - Instituto de Biologia Molecular (IBMC), Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-6899","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Instituto de Inova\u00e7\u00e3o e Investiga\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Neurobiologia Molecular - Instituto de Biologia Molecular (IBMC), Universidade do Porto, R. 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