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Alpha-synuclein levels in multiple sclerosis patients with restless leg syndrome

Year 2020, Volume: 45 Issue: 2, 562 - 567, 30.06.2020
https://doi.org/10.17826/cumj.674564

Abstract

Purpose: The restless legs syndrome is more frequent and critical in Multiple Sclerosis patients, and it harms their general well-being and life quality. Alpha-synuclein is a synuclein protein that can have an impact on the pathway of signaling, affecting the Dopamin 2 receptor and its receptor trafficking. Studies have shown that the decrease in dopamine 2 receptor and Restless Legs Syndrome disease are correlated. This study is aimed to ascertain the alpha-synuclein level in multiple sclerosis patients with restless legs syndrome.
Materials and Methods: We took blood samples from 40 multiple sclerosis patients and 20 healthy individuals. Half of the patient group had Multiple Sclerosis with restless leg syndrome. In the study groups, the alpha-synuclein level was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-dependent immunosorbent assay (ELISA).
Results: Alpha-synuclein gene expression level was found or be significantly lower in restless leg syndrome patients with multiple sclerosis than the Alpha-synuclein gene expression level in the control group.
Conclusion: Alpha-synuclein may have an impact on the pathogenesis of the restless leg syndrome of multiple sclerosis disease. Further investigations are required to determine the impact of alpha-synuclein in the pathogenesis of restless leg syndrome in multiple sclerosis disease.

Supporting Institution

This work was supported by Çanakkale Onsekiz Mart University The Scientific Research Coordination Unit, Project number:

Project Number

TSA-2018-1414

References

  • Carnero Contentti E, Lopez PA, Nadur D, Balbuena ME, Finkelstein AM, Tkachuk V. Impact, Frequency, and Severity of Restless Legs Syndrome in Patients with Multiple Sclerosis in Argentina. International journal of MS care. 2019;21(4):157-165.
  • Kurt S. The Comorbidity of Migraine and Restless Legs Syndrome. Current neurology and neuroscience reports. 2019;19(9):60.
  • Romigi A, Vitrani G, Caccamo M, Centonze D. Restless Legs Syndrome Related to Vortioxetine: A Case Report. Journal of clinical psychopharmacology. 2019;39(5):514-516.
  • Kidd PM. Multiple sclerosis, an autoimmune inflammatory disease: prospects for its integrative management. Alternative medicine review : a journal of clinical therapeutic. 2001;6(6):540-566.
  • Matute-Blanch C, Montalban X, Comabella M. Multiple sclerosis, and other demyelinating and autoimmune inflammatory diseases of the central nervous system. Handbook of clinical neurology. 2017;146:67-84.
  • Albertsdottir A, Sigurdardottir AK, Thorleifsdottir B. [Prevalence of Poor Sleep Quality and Sleep Disturbances in Icelanders with Multiple Sclerosis]. Laeknabladid. 2019;105(9):379-384.
  • Cederberg KLJ, Jeng B, Sasaki JE, Braley TJ, Walters AS, Motl RW. Restless legs syndrome and health-related quality of life in adults with multiple sclerosis. Journal of sleep research. 2019:e12880.
  • Lebrato Hernandez L, Prieto Leon M, Cerda Fuentes NA, Ucles Sanchez AJ, Casado Chocan JL, Diaz Sanchez M. Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact. Neurologia (Barcelona, Spain). 2019.
  • Giannaki CD, Aristotelous P, Stefanakis M, et al. Restless legs syndrome in Multiple Sclerosis patients: a contributing factor for fatigue, impaired functional capacity, and diminished health-related quality of life. Neurological research. 2018;40(7):586-592.
  • Wang H, Wang K, Xu W, et al. Cerebrospinal fluid alpha-synuclein levels are elevated in multiple sclerosis and neuromyelitis optica patients during replase. Journal of neurochemistry. 2012;122(1):19-23.
  • Clayton DF, George JM. Synucleins in synaptic plasticity and neurodegenerative disorders. Journal of neuroscience research. 1999;58(1):120-129.
  • Roodveldt C, Labrador-Garrido A, Gonzalez-Rey E, et al. Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: differences between wild-type and Parkinson's disease-linked mutants. PloS one. 2010;5(10):e13481.
  • Austin SA, Floden AM, Murphy EJ, Combs CK. Alpha-synuclein expression modulates microglial activation phenotype. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(41):10558-10563.
  • Shameli A, Xiao W, Zheng Y, et al. A critical role for alpha-synuclein in development and function of T lymphocytes. Immunobiology. 2016;221(2):333-340.
  • Xiao W, Shameli A, Harding CV, Meyerson HJ, Maitta RW. Late stages of hematopoiesis and B cell lymphopoiesis are regulated by alpha-synuclein, a key player in Parkinson's disease. Immunobiology. 2014;219(11):836-844.
  • Papadopoulos D, Ewans L, Pham-Dinh D, Knott J, Reynolds R. Upregulation of alpha-synuclein in neurons and glia in inflammatory demyelinating disease. Molecular and cellular neurosciences. 2006;31(4):597-612.
  • Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology. 2011;69(2):292-302.
  • Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep medicine. 2003;4(2):101-119.
  • Veauthier C. Sleep disorders in multiple sclerosis. Review. Current neurology and neuroscience reports. 2015;15(5):21.
  • Liu G, Feng X, Lan C, et al. Restless leg syndrome and multiple sclerosis: a case-control study in China. Sleep & breathing = Schlaf & Atmung. 2015;19(4):1355-1360.
  • Li Y, Munger KL, Batool-Anwar S, De Vito K, Ascherio A, Gao X. Association of multiple sclerosis with restless legs syndrome and other sleep disorders in women. Neurology. 2012;78(19):1500-1506.
  • Dehay B, Bourdenx M, Gorry P, et al. Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations. Lancet Neurol. 2015;14(8):855-866.
  • Lu JQ, Fan Y, Mitha AP, et al. Association of alpha-synuclein immunoreactivity with inflammatory activity in multiple sclerosis lesions. Journal of neuropathology and experimental neurology. 2009;68(2):179-189.
  • Mejia M, Rodriguez-Leyva I, Cortes-Enriquez F, et al. Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: a pilot cross-sectional study. Journal of the neurological sciences. Jan 15 2019;396:87-93.
  • Lahut S, Vadasz D, Depboylu C, et al. The PD-associated alpha-synuclein promoter Rep1 allele 2 shows diminished frequency in restless legs syndrome. Neurogenetics. 2014;15(3):189-192.
  • Tan EK, Chandran VR, Fook-Chong S, et al. Alpha-synuclein mRNA expression in sporadic Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society. 2005;20(5):620-623.
  • Lee PH, Lee G, Park HJ, Bang OY, Joo IS, Huh K. The plasma alpha-synuclein levels in patients with Parkinson's disease and multiple system atrophy. Journal of neural transmission (Vienna, Austria : 1996). 2006;113(10):1435-1439.
  • Li QX, Mok SS, Laughton KM, et al. Plasma alpha-synuclein is decreased in subjects with Parkinson's disease. Experimental neurology. 2007;204(2):583-588.
  • Shi M, Zabetian CP, Hancock AM, et al. Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease. Neuroscience letters. 2010;480(1):78-82.

Huzursuz bacak sendromu olan multipl sklerozlu hastalarda alfa-sinüklein düzeyleri

Year 2020, Volume: 45 Issue: 2, 562 - 567, 30.06.2020
https://doi.org/10.17826/cumj.674564

Abstract

Amaç: Huzursuz Bacak Sendromu, multipl skleroz hastalığında yaygın olarak görülmektedir, ayrıca hastaların genel sağlığı ve yaşam kalitesi üzerinde olumsuz bir etkisi vardır. Alfa-sinüklein, Dopamin 2 reseptörünün sinyal yolağında önemli bir rol oynamaktadır. Çalışmalar, dopamin 2 reseptörü ve huzursuz bacak sendromu hastalığı arasında ilişki olduğunu göstermiştir. Bu çalışma huzursuz bacak sendromlu multipl skleroz hastalarında alfa-sinükleinin düzeyini belirlemek amacıyla yapılmıştır.
Gereç ve Yöntem: Bu çalışmada 40 multipl skleroz hastasından ve 20 sağlıklı bireyden kan örneği alındı. Hasta grubunun yarısı huzursuz bacak sendromlu multipl skleroz hastalarından oluşmaktadır. Çalışma gruplarında alfa sinüklein düzeyi enzime bağlı immünosorbent kit (ELISA) ve gerçek zamanlı kantitatif polimeraz zincir reaksiyonu (qRT-PCR) metodu kullanılarak belirlendi.
Bulgular: Huzursuz bacak sendromlu multipl skleroz hastalarında alfa-sinüklein gen ekspresyon düzeyi kontrol grubuna göre anlamlı düzeyde düşük bulundu.
Sonuç: Alfa-sinüklein multipl skleroz hastalığında huzursuz bacak sendromu patogenezinde etkili olabilir. Multipl skleroz hastalığında huzursuz bacak sendromu patogenezinde alfa-sinükleinin rolünü belirlemek için daha fazla çalışmaya ihtiyaç vardır.

Project Number

TSA-2018-1414

References

  • Carnero Contentti E, Lopez PA, Nadur D, Balbuena ME, Finkelstein AM, Tkachuk V. Impact, Frequency, and Severity of Restless Legs Syndrome in Patients with Multiple Sclerosis in Argentina. International journal of MS care. 2019;21(4):157-165.
  • Kurt S. The Comorbidity of Migraine and Restless Legs Syndrome. Current neurology and neuroscience reports. 2019;19(9):60.
  • Romigi A, Vitrani G, Caccamo M, Centonze D. Restless Legs Syndrome Related to Vortioxetine: A Case Report. Journal of clinical psychopharmacology. 2019;39(5):514-516.
  • Kidd PM. Multiple sclerosis, an autoimmune inflammatory disease: prospects for its integrative management. Alternative medicine review : a journal of clinical therapeutic. 2001;6(6):540-566.
  • Matute-Blanch C, Montalban X, Comabella M. Multiple sclerosis, and other demyelinating and autoimmune inflammatory diseases of the central nervous system. Handbook of clinical neurology. 2017;146:67-84.
  • Albertsdottir A, Sigurdardottir AK, Thorleifsdottir B. [Prevalence of Poor Sleep Quality and Sleep Disturbances in Icelanders with Multiple Sclerosis]. Laeknabladid. 2019;105(9):379-384.
  • Cederberg KLJ, Jeng B, Sasaki JE, Braley TJ, Walters AS, Motl RW. Restless legs syndrome and health-related quality of life in adults with multiple sclerosis. Journal of sleep research. 2019:e12880.
  • Lebrato Hernandez L, Prieto Leon M, Cerda Fuentes NA, Ucles Sanchez AJ, Casado Chocan JL, Diaz Sanchez M. Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact. Neurologia (Barcelona, Spain). 2019.
  • Giannaki CD, Aristotelous P, Stefanakis M, et al. Restless legs syndrome in Multiple Sclerosis patients: a contributing factor for fatigue, impaired functional capacity, and diminished health-related quality of life. Neurological research. 2018;40(7):586-592.
  • Wang H, Wang K, Xu W, et al. Cerebrospinal fluid alpha-synuclein levels are elevated in multiple sclerosis and neuromyelitis optica patients during replase. Journal of neurochemistry. 2012;122(1):19-23.
  • Clayton DF, George JM. Synucleins in synaptic plasticity and neurodegenerative disorders. Journal of neuroscience research. 1999;58(1):120-129.
  • Roodveldt C, Labrador-Garrido A, Gonzalez-Rey E, et al. Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: differences between wild-type and Parkinson's disease-linked mutants. PloS one. 2010;5(10):e13481.
  • Austin SA, Floden AM, Murphy EJ, Combs CK. Alpha-synuclein expression modulates microglial activation phenotype. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(41):10558-10563.
  • Shameli A, Xiao W, Zheng Y, et al. A critical role for alpha-synuclein in development and function of T lymphocytes. Immunobiology. 2016;221(2):333-340.
  • Xiao W, Shameli A, Harding CV, Meyerson HJ, Maitta RW. Late stages of hematopoiesis and B cell lymphopoiesis are regulated by alpha-synuclein, a key player in Parkinson's disease. Immunobiology. 2014;219(11):836-844.
  • Papadopoulos D, Ewans L, Pham-Dinh D, Knott J, Reynolds R. Upregulation of alpha-synuclein in neurons and glia in inflammatory demyelinating disease. Molecular and cellular neurosciences. 2006;31(4):597-612.
  • Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology. 2011;69(2):292-302.
  • Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep medicine. 2003;4(2):101-119.
  • Veauthier C. Sleep disorders in multiple sclerosis. Review. Current neurology and neuroscience reports. 2015;15(5):21.
  • Liu G, Feng X, Lan C, et al. Restless leg syndrome and multiple sclerosis: a case-control study in China. Sleep & breathing = Schlaf & Atmung. 2015;19(4):1355-1360.
  • Li Y, Munger KL, Batool-Anwar S, De Vito K, Ascherio A, Gao X. Association of multiple sclerosis with restless legs syndrome and other sleep disorders in women. Neurology. 2012;78(19):1500-1506.
  • Dehay B, Bourdenx M, Gorry P, et al. Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations. Lancet Neurol. 2015;14(8):855-866.
  • Lu JQ, Fan Y, Mitha AP, et al. Association of alpha-synuclein immunoreactivity with inflammatory activity in multiple sclerosis lesions. Journal of neuropathology and experimental neurology. 2009;68(2):179-189.
  • Mejia M, Rodriguez-Leyva I, Cortes-Enriquez F, et al. Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: a pilot cross-sectional study. Journal of the neurological sciences. Jan 15 2019;396:87-93.
  • Lahut S, Vadasz D, Depboylu C, et al. The PD-associated alpha-synuclein promoter Rep1 allele 2 shows diminished frequency in restless legs syndrome. Neurogenetics. 2014;15(3):189-192.
  • Tan EK, Chandran VR, Fook-Chong S, et al. Alpha-synuclein mRNA expression in sporadic Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society. 2005;20(5):620-623.
  • Lee PH, Lee G, Park HJ, Bang OY, Joo IS, Huh K. The plasma alpha-synuclein levels in patients with Parkinson's disease and multiple system atrophy. Journal of neural transmission (Vienna, Austria : 1996). 2006;113(10):1435-1439.
  • Li QX, Mok SS, Laughton KM, et al. Plasma alpha-synuclein is decreased in subjects with Parkinson's disease. Experimental neurology. 2007;204(2):583-588.
  • Shi M, Zabetian CP, Hancock AM, et al. Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease. Neuroscience letters. 2010;480(1):78-82.
There are 29 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Suat Çakına 0000-0002-3990-7641

Selma Yücel 0000-0001-5139-1791

Cemre Çağan Polat This is me 0000-0002-7323-3169

Şamil Öztürk 0000-0002-9435-8139

Project Number TSA-2018-1414
Publication Date June 30, 2020
Acceptance Date March 25, 2020
Published in Issue Year 2020 Volume: 45 Issue: 2

Cite

MLA Çakına, Suat et al. “Alpha-Synuclein Levels in Multiple Sclerosis Patients With Restless Leg Syndrome”. Cukurova Medical Journal, vol. 45, no. 2, 2020, pp. 562-7, doi:10.17826/cumj.674564.