Propranolol significantly reduced DNA polymerase β expression in patients with essential tremor

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Nefise Kandemir
Sercan Kenanoglu
Murat Gultekin
Nuriye Gokce
Hilal Akalin
Nazife Taşçıoğlu
Meral Mirza
Emel Koseoglu
Munis Dundar


Essential tremor (ET) is the most common movement disorder. Propranolol is a first-line medication for ET. We aimed to evaluate the effect of propranolol on the expression of poly (ADP-ribose) polymerase 1 (PARP1) and DNA polymerase beta (POLB) genes, which are known to be related to neurodegenerative diseases, in patients with ET.

Thirty-five healthy volunteers and thirty-five patients followed up with essential tremors were included in a non-randomized control experimental study. Expressions of PARP1 and POLB genes were compared between the control group and the patient group. In addition, pre- and post-treatment gene expression levels and Fahn-Tolosa-Marin tremor scale values of the patient group were compared after 8 weeks of propranolol treatment. The Wilcoxon rank and Mann Whitney U tests were used to analyze the data.

At baseline, PARP1 expression was significantly lower in the ET group than in the control group. (p<0.001). POLB gene expression was significantly higher in the pre-treatment ET group than in the controls (p<0.05). There was no significant difference in PARP1 expression levels before and after 8 weeks of propranolol treatment. POLB gene expression was significantly higher in the pre-treatment group than in the post-treatment group (p<0.001).

Propranolol significantly decreased POLB gene expression but there was no significant difference in PARP1 gene expression levels in the patient group, after 8 weeks of propranolol treatment.

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How to Cite
Kandemir, N. ., Kenanoglu, S. ., Gultekin, M. ., Gokce, N. ., Akalin, H. ., Taşçıoğlu, . N. ., Mirza, M. ., Koseoglu, E. ., & Dundar, M. . (2021). Propranolol significantly reduced DNA polymerase β expression in patients with essential tremor. Universa Medicina, 40(3), 207–215.
Original Articles
Author Biographies

Nefise Kandemir, Department of Medical Genetics, Erciyes University Faculty of Medicine, Kayseri, Turkey

Department of Medical Genetics, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey

Hilal Akalin, Department of Medical Genetics, Erciyes University Faculty of Medicine, Kayseri, Turkey

Department of Medical Genetics, Ahi Evran University Faculty of Medicine, Kirsehir, Turkey


Louis ED. Treatment of essential tremor: are there issues we are looking for? Front Neurol 2012;2:1-8. doi: 10.3389/fneur.2011.00091.

Louis ED. Age of onset: can we rely on essential tremor patients to report this? Data from a prospective, longitudinal study. Neuroepidemiology 2013;40:93-8. DOI: 10.1159/000341903.

Louis ED, Gerbin M, Galecki M. Essential tremor 10, 20, 30, 40: clinical snapshots of the disease by decade of duration. Eur J Neurol 2013; 20: 949-54. DOI: 10.1111/ene.12123.

Prasad S, Bhalsing KS, Hunjhunwala K, Lenka A, Binu VS, Pal PK. Phenotypic variability of essential tremor based on the age at onset. Canadian J Neurol Sci 2019; 46: 192-8. DOI: 10.1017/cjn.2018.384.

Taylor GS. Essential tremor: a review. 2021. Honors Projects. 814.

Jiménez‐Jiménez F, Alonso-Navarro H, García-Martín E, Lorenzo-Betancor O, Pastor P, Agúndez JAG. Update on genetics of essential tremor. Acta Neurol Scand 2013;128:359-71. DOI: 10.1111/ane.12148.

Louis ED, McCreary M. How common is essential tremor? Update on the worldwide prevalence of essential tremor. Tremor Other Hyperkinetic Movements 2021;11:28. DOI: 10.5334/tohm.632.

Kuhlenbäumer GF , Hopfner F, Deuschl G. Genetics of essential tremor: meta-analysis and review. Neurology 2014;82:1000-7. DOI: 10.1212/WNL.0000000000000211.

Louis ED, Babij R, Ma K, Cortés E, Vonsattel JPG. Essential tremor followed by progressive supranuclear palsy: postmortem reports of 11 patients. J Neuropathol Exp Neurol 2013;72:8-17. DOI: 10.1097/NEN.0b013e31827ae56e.

Kandemir N, Gultekin M, Kara M, et al. Propranolol decreases DRD3 and SLC1A2 gene expression in patients with essential tremor. Univ Med 2020;39:105-12. doi: 10.18051/UnivMed.2020.v39.10.

Tio M, Tan EK. Genetics of essential tremor. Parkinsonism Relat Disord 2016;22 Suppl 1:S176-S8.DOI: 10.1016/j.parkreldis.2015.09.022.

Ondo WG. Current and emerging treatments of essential tremor. Neurol Clin 2020;38:309-23. DOI: 10.1016/j.ncl.2020.01.002.

Morales J, Li L, Fattah FJ, et al. Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr 2014;24:15-28. DOI: 10.1615/critreveukaryotgeneexpr.2013006875.

Swindall AF, Stanley JA, Yang ES. PARP-1: friend or foe of DNA damage and repair in tumorigenesis? Cancers 2013;5:943-58. doi: 10.3390/cancers503094.3

Hoch NC, Polo LM. ADP-ribosylation: from molecular mechanisms to human disease. Genet Mol Biol 2020;43(1 Suppl 1):e20190075. DOI: 10.1590/1678-4685-GMB-2019-0075.

Zhou T, Pan F, Cao Y, et al. R152C DNA Pol β mutation impairs base excision repair and induces cellular transformation. Oncotarget 2016;7:6902–15. DOI: 10.18632/oncotarget.6849.

Fahn S, Tolosa E, Marín C. Clinical rating scale for tremor. In: Jankovic J, Tolosa E, editors. Parkinson’s disease and movement disorders. 2nd. ed. Baltimore: Williams & Wilkins; 1993. p. 225-3.

Cersonsky TEK, Kellner S, Morganet S, et al. Demoralization in essential tremor: prevalence, clinical correlates, and dissociation from tremor severity. CNS Spectr 2020 ;25:16-23.. DOI: 10.1017/S1092852918001633.

Alonso-Navarro H, García-Martín E, Agúndez JAG, Jiménez-Jiménez FJ. Association between restless legs syndrome and other movement disorders. Neurology 2019;92:948-64. DOI: 10.1212/WNL.0000000000007500.

Diez-Fairen M, Bandres-Ciga S, Houle G, et al. Genome-wide estimates of heritability and genetic correlations in essential tremor. Parkinsonism Relat Disord 2019;64:262-7. DOI: 10.1016/j.parkreldis.2019.05.002.

Hopfner F, Helmich RC. The etiology of essential tremor: genes versus environent. Parkinsonism Relat Disord 2018;46 Suppl 1:S92-S6. doi: 10.1016/j.parkreldis.2017.07.014.

Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E. Álvarez I, Pastor P, Agúndez JAG. Genomic markers for essential tremor. Pharmaceuticals 2021;14:516.

Liao C, Sarayloo F, Rochefort D, et al. Multiomics analyses identify genes and pathways relevant to essential tremor. Mov Disord 2020;35:1153-62. doi: 10.1002/mds.28031.

Shanker V. Essential tremor: diagnosis and management. BMJ 2019;366:l4485. doi: 10.1136/bmj.l4485.

Hopfner F, Höglinger GU, Kuhlenbäumer G, et al. β-adrenoreceptors and the risk of Parkinson's disease. Lancet Neurology 2020;19:247-54. DOI: 10.1016/S1474-4422(19)30400-4.

Fatokun AA, Dawson VL, Dawson TM. Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities. Br J Pharmacol 2014;71:2000-16. doi: 10.1111/bph.12416.

Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL, Bohr VA. DNA damage, DNA repair, aging, and neurodegeneration. Cold Spring Harb Perspect Med 2015;18:a025130. doi: 10.1101/cshperspect.a025130.

Fang EF, Scheibye-Knudsen M, Brace LE, et al. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell 2014;157:882-96. doi: 10.1016/j.cell.2014.03.026.

Anandhan A, Jacome MS, Lei S, et al. Metabolic dysfunction in Parkinson's disease: bioenergetics, redox homeostasis and central carbon etabolism. Brain Res Bull 2017;133:12-30. doi: 10.1016/j.brainresbull.2017.03.009.

Brighina L, Rivab C Bertola F,et al. Association analysis of PARP1 polymorphisms with Parkinson’s disease. Parkinsonism Rel Disord 2011;17:701-4. 10.1016/j.parkreldis.2011.06.022.

Alemasova EE, Lavrik OI. Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins. Nucleic Acids Res 2019;47:3811-27. doi: 10.1093/nar/gkz120.

Adamczyk A, Kaźmierczak A, Czapski GA, Strosznajder JB. Alpha-synuclein induced cell death in mouse hippocampal (HT22) cells is mediated by nitric oxide-dependent activation of caspase-3. FEBS Lett 2010;584:3504-8. doi: 10.1016/j.febslet.2010.07.019.

Kamal SJ, Khadhim HM. Effects of Irbesartan in induced Parkinson’s disease in mice. Int J Pharmaceut Qual Assur 2021;12:31-9. DOI: 10.25258/ijpqa.12.1.5.

Renani PG, Taheri F, Rostami D, et al. Involvement of aberrant regulation of epigenetic mechanisms in the pathogenesis of Parkinson's disease and epigenetic-based therapies. J Cell Physiol 2019;234:19307-19. doi: 10.1002/jcp.28622.

Broniowska KA, Diers AR, Corbett JA, Hogg N. Effect of nitric oxide on naphthoquinone toxicity in endothelial cells: role of bioenergetic dysfunction and poly (ADP-ribose) polymerase activation. Biochemistry 2013;52:4364-72. doi: 10.1021/bi400342t.

Maciag AE, Holland RJ, Kim Y, et al. Nitric oxide (NO) releasing poly ADP-ribose polymerase 1 (PARP-1) inhibitors targeted to glutathione S-transferase P1-overexpressing cancer cells. J Med Chem 2014;57:2292-302. doi: 10.1021/jm401550d.

Krokan HE, Bjøras M. Base excision repair. Cold Spring Harb Perspect Biol 2013;5:a012583. doi: 10.1101/cshperspect.a012583.

Beard WA, Wilson SH. DNA polymerase beta and other gap-filling enzymes in mammalian base excision repair. Enzymes 2019;45:1-26. doi: 10.1016/bs.enz.2019.08.002.

Wang H, Chen Y, Chen J, Cell cycle regulation of DNA polymerase beta in rotenone-based Parkinson's disease models. PLoS One 2014;9:e109697. doi: 10.1371/journal.pone.0109697.