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Its hallmarks are cutaneous findings including neurofibromas, benign peripheral nerve sheath tumors. We analyzed the collagen and matrix metalloproteinase 1 (MMP1) expression in Neurofibromatosis 1 cutaneous neurofibroma and found excessive expression of collagen and reduced expression of MMP1. To identify new therapeutic drugs for neurofibroma, we analyzed phosphorylation of components of the Ras pathway, which underlies NF1 regulation, and applied treatments to block this pathway (PD184352, U0126, and rapamycin) and lysosomal processes (chloroquine (CQ), hydroxychloroquine (HCQ), and bafilomycin A (BafA)) in cultured Neurofibromatosis 1 fibroblasts. We found that downregulation of the MMP1 protein was a key abnormal feature in the neurofibromatosis 1 fibroblasts and that the decreased MMP1 was restored by the lysosomal blockers CQ and HCQ, but not by the blockers of the Ras pathway. Moreover, the MMP1-upregulating activity of those lysosomal blockers was dependent on aryl hydrocarbon receptor (AHR) activation and ERK phosphorylation. Our findings suggest that lysosomal blockers are potential candidates for the treatment of Neurofibromatosis 1 neurofibroma.<\/jats:p>","DOI":"10.1038\/s41419-021-03802-9","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T18:15:24Z","timestamp":1621448124000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Metalloproteinase 1 downregulation in neurofibromatosis 1: Therapeutic potential of antimalarial hydroxychloroquine and chloroquine"],"prefix":"10.1038","volume":"12","author":[{"given":"Gaku","family":"Tsuji","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-8965","authenticated-orcid":false,"given":"Ayako","family":"Takai-Yumine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masutaka","family":"Furue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"3802_CR1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/ajmg.a.33139","volume":"152A","author":"DG Evans","year":"2010","unstructured":"Evans, D. 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