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Review

Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies

1
Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland
2
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil
*
Authors to whom correspondence should be addressed.
Academic Editor: Ivano Condò
Int. J. Mol. Sci. 2021, 22(12), 6545; https://doi.org/10.3390/ijms22126545
Received: 31 May 2021 / Revised: 13 June 2021 / Accepted: 14 June 2021 / Published: 18 June 2021
Huntington’s 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. View Full-Text
Keywords: purine metabolism; purinergic signaling; Huntington’s disease purine metabolism; purinergic signaling; Huntington’s disease
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MDPI and ACS Style

Tomczyk, M.; Glaser, T.; Slominska, E.M.; Ulrich, H.; Smolenski, R.T. Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies. Int. J. Mol. Sci. 2021, 22, 6545. https://doi.org/10.3390/ijms22126545

AMA Style

Tomczyk M, Glaser T, Slominska EM, Ulrich H, Smolenski RT. Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies. International Journal of Molecular Sciences. 2021; 22(12):6545. https://doi.org/10.3390/ijms22126545

Chicago/Turabian Style

Tomczyk, Marta, Talita Glaser, Ewa M. Slominska, Henning Ulrich, and Ryszard T. Smolenski. 2021. "Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies" International Journal of Molecular Sciences 22, no. 12: 6545. https://doi.org/10.3390/ijms22126545

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