{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:22:47Z","timestamp":1784395367279,"version":"3.55.0"},"reference-count":128,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre of Poland","award":["2016\/22\/M\/NZ4\/00678"],"award-info":[{"award-number":["2016\/22\/M\/NZ4\/00678"]}]},{"name":"S\u00e2o Paulo Research Foundation FAPESP","award":["2018\/07366-4"],"award-info":[{"award-number":["2018\/07366-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a multi-system disorder that is caused by expanded CAG repeats within the exon-1 of the huntingtin (HTT) gene that translate to the polyglutamine stretch in the HTT protein. HTT interacts with the proteins involved in gene transcription, endocytosis, and metabolism. HTT may also directly or indirectly affect purine metabolism and signaling. We aimed to review existing data and discuss the modulation of the purinergic system as a new therapeutic target in HD. Impaired intracellular nucleotide metabolism in the HD affected system (CNS, skeletal muscle and heart) may lead to extracellular accumulation of purine metabolites, its unusual catabolism, and modulation of purinergic signaling. The mechanisms of observed changes might be different in affected systems. Based on collected findings, compounds leading to purine and ATP pool reconstruction as well as purinergic receptor activity modulators, i.e., P2X7 receptor antagonists, may be applied for HD treatment.<\/jats:p>","DOI":"10.3390\/ijms22126545","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T11:19:20Z","timestamp":1624015160000},"page":"6545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Purine Nucleotides Metabolism and Signaling in Huntington\u2019s Disease: Search for a Target for Novel Therapies"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-9748","authenticated-orcid":false,"given":"Marta","family":"Tomczyk","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talita","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3037-1844","authenticated-orcid":false,"given":"Ewa M.","family":"Slominska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2114-3815","authenticated-orcid":false,"given":"Henning","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard T.","family":"Smolenski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1177\/0891988710383573","article-title":"The Clinical and Genetic Features of Huntington Disease","volume":"23","author":"Sturrock","year":"2010","journal-title":"J. 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