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HD is a hereditary disease caused by mutations in the Huntingtin\u2019s (HTT) gene and characterized by neurodegeneration and motor and behavioral symptoms that are associated with activation of dopamine receptors. We explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients and examined the effects of nilotinib on several brain mechanisms, including dopamine transmission and gene expression via cerebrospinal fluid (CSF) miRNA sequencing. Nilotinib, 150 mg, did not result in any behavioral changes, although it significantly attenuated HVA levels, suggesting reduction of dopamine catabolism. There was no significant change in HTT, phosphorylated neuro-filament and inflammatory markers in the CSF and plasma via immunoassays. Whole miRNA genome sequencing of the CSF revealed significant longitudinal changes in miRNAs that control specific genes associated with autophagy, inflammation, microglial activity and basal ganglia neurotransmitters, including dopamine and serotonin.<\/jats:p>","DOI":"10.3390\/metabo12121225","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T01:47:46Z","timestamp":1670377666000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington\u2019s Disease Patients"],"prefix":"10.3390","volume":"12","author":[{"given":"Karen E.","family":"Anderson","sequence":"first","affiliation":[{"name":"MedStar Georgetown University Hospital Huntington\u2019s Disease Research, Education and Care Center, Department of Psychiatry and Department of Neurology, Georgetown University Medical Center, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rency","family":"Varghese","sequence":"additional","affiliation":[{"name":"Genomics and Epigenomics Shared Resource, Department of Oncology, Georgetown University Medical Center, Building D, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaeline L.","family":"Hebron","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8693-0409","authenticated-orcid":false,"given":"Erin","family":"Koppel","sequence":"additional","affiliation":[{"name":"MedStar Georgetown University Hospital Huntington\u2019s Disease Research, Education and Care Center, Department of Psychiatry and Department of Neurology, Georgetown University Medical Center, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"McCartin","sequence":"additional","affiliation":[{"name":"MedStar Georgetown University Hospital Huntington\u2019s Disease Research, Education and Care Center, Department of Psychiatry and Department of Neurology, Georgetown University Medical Center, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6264-8425","authenticated-orcid":false,"given":"Robin","family":"Kuprewicz","sequence":"additional","affiliation":[{"name":"MedStar Georgetown University Hospital Huntington\u2019s Disease Research, Education and Care Center, Department of Psychiatry and Department of Neurology, Georgetown University Medical Center, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Matar","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2012-7063","authenticated-orcid":false,"given":"Charbel","family":"Moussa","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd, NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes. 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