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Immunomodulatory and anti-protein aggregation properties of tetracyclines were demonstrated in several disease models. In the present study, the neuroprotective and anti-inflammatory effects of the tetracycline doxycycline were investigated in the mouse model of HD disease R6\/2. Transgenic mice were daily treated with doxycycline 20\u00a0mg\/kg, starting from 4\u00a0weeks of age. After sacrifice, histological and immunohistochemical studies were performed. We found that doxycycline-treated R6\/2 mice survived longer and displayed less severe signs of neurological dysfunction than the saline-treated ones. Primary outcome measures such as striatal atrophy, neuronal intranuclear inclusions, and the negative modulation of microglial reaction revealed a neuroprotective effect of the compound. Doxycycline provided a significantly increase of activated CREB and BDNF in the striatal neurons, along with a down modulation of neuroinflammation, which, combined, might explain the beneficial effects observed in this model. Our findings show that doxycycline treatment could be considered as a valid therapeutic approach for HD.<\/jats:p>","DOI":"10.1007\/s12035-019-01847-8","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T09:02:17Z","timestamp":1577350937000},"page":"1889-1903","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Neuroprotective Effects of Doxycycline in the R6\/2 Mouse Model of Huntington\u2019s Disease"],"prefix":"10.1007","volume":"57","author":[{"given":"Emanuela","family":"Paldino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Balducci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"La Vitola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Artioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"D\u2019Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Giamp\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimiro","family":"Artuso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Forloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-523X","authenticated-orcid":false,"given":"Francesca R.","family":"Fusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"1847_CR1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nrd.2015.14","volume":"15","author":"K Biber","year":"2016","unstructured":"Biber K, M\u00f6ller T, Boddeke E, Prinz M (2016) Central nervous system myeloid cells as drug targets: current status and translational challenges. 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