Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies
Huntington’s disease (HD) is a multi-system disorder that is caused by expanded CAG repeats within the exon-1 of the huntingtin (<i>HTT</i>) gene that translate to the polyglutamine stretch in the HTT protein. HTT interacts with the proteins involved in gene transcription, endocytosis, a...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/12/6545 |
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| author | Marta Tomczyk Talita Glaser Ewa M. Slominska Henning Ulrich Ryszard T. Smolenski |
| author_facet | Marta Tomczyk Talita Glaser Ewa M. Slominska Henning Ulrich Ryszard T. Smolenski |
| author_sort | Marta Tomczyk |
| collection | DOAJ |
| description | Huntington’s disease (HD) is a multi-system disorder that is caused by expanded CAG repeats within the exon-1 of the huntingtin (<i>HTT</i>) 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. |
| first_indexed | 2024-03-10T10:18:06Z |
| format | Article |
| id | doaj.art-f8ca967c2eeb44b0aca7dd6484157c2f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:18:06Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f8ca967c2eeb44b0aca7dd6484157c2f2023-11-22T00:41:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212654510.3390/ijms22126545Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel TherapiesMarta Tomczyk0Talita Glaser1Ewa M. Slominska2Henning Ulrich3Ryszard T. Smolenski4Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, BrazilDepartment of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, PolandDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, BrazilDepartment of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, PolandHuntington’s disease (HD) is a multi-system disorder that is caused by expanded CAG repeats within the exon-1 of the huntingtin (<i>HTT</i>) 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.https://www.mdpi.com/1422-0067/22/12/6545purine metabolismpurinergic signalingHuntington’s disease |
| spellingShingle | Marta Tomczyk Talita Glaser Ewa M. Slominska Henning Ulrich Ryszard T. Smolenski Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies International Journal of Molecular Sciences purine metabolism purinergic signaling Huntington’s disease |
| title | Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies |
| title_full | Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies |
| title_fullStr | Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies |
| title_full_unstemmed | Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies |
| title_short | Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies |
| title_sort | purine nucleotides metabolism and signaling in huntington s disease search for a target for novel therapies |
| topic | purine metabolism purinergic signaling Huntington’s disease |
| url | https://www.mdpi.com/1422-0067/22/12/6545 |
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