M.A. Mukhamedyarov a, E.O. Petukhova a, E.A. Ushanova a,b, D.F. Nurkhametova b, A.V. Leushina a, A. Palotás c, A.L. Zefirov a
a Kazan State Medical University, Kazan, 420012 Russia
b Kazan Federal University, Kazan, 420008 Russia
c Private Medical Practice and Research Center “Asklepios-Med”, Szeged, H-6722 Hungary
Abstract
Neurodegenerative disorders (NDD) – Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis – affect about 10% of the elderly population worldwide, which makes them one of the most important medical and social problems. Numerous literature data confirm that NDD are related not only to CNS dysfunction, but also to dysregulation and pathological changes in peripheral tissues (neuromuscular synapses, skeletal, and cardiac muscles). These peripheral disorders may be important in the NDD pathogenesis by contributing to the pathological processes that directly lead to disability and death of patients (atrophy and paralysis of skeletal muscle, myocardial infarction, etc.). Notably, the pathology of neuromuscular and cardiovascular systems in NDD is currently underestimated und insufficiently studied, but it is not merely a “reflection” of degenerative changes in the nervous system, being rather a separate aspect of the pathogenesis of NDD. Several studies showed that peripheral dysfunctions in NDD can be either primary and/or reinforce degeneration in CNS, which further increases their importance in the development of the disease. In this paper, we reviewed the available literature data on the peripheral dysfunctions in NDD and their contribution to NDD pathogenesis.
Keywords: neurodegenerative diseases, Alzheimer’s disease, neuromuscular system, peripheral dysfunction
Acknowledgements. The study was supported by the Russian Foundation for Basic Research (RFBR) (project no. 17-04-02175), joint grant of the RFBR and the Academy of Sciences of Tatarstan Republic (project no. 18-415-160016), scholarship of the President of the Russian Federation for young researchers and scientists (no. SP-255.2016.4), grant of the President of the Russian Federation for the support of young doctors of science (project no. MD-6877.2018.4). The part of study regarding the dysfunction of neuromuscular synapses in neurodegenerative disorders (section “Dysfunction of Neuromuscular Synapses in Neurodegenerative Disorders”) was supported by the Russian Science Foundation (project no. 14-15-00847).
References
1. Prince M., Bryce R., Albanese E., Wimo A., Ribeiro W., Ferri C.P. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimer's Dementia, 2013, vol. 9, no. 1, pp. 63–75.e2. doi: 10.1016/j.jalz.2012.11.007.
2. Mukhamedyarov M.A., Zefirov A.L. The influence of beta-amyloid peptide on the functions of excitable tissues: Physiological and pathological aspects. Usp. Fiziol. Nauk, 2013, vol. 44, no. 1, pp. 55–71. (In Russian)
3. Ugrumov M.V. Development of preclinical diagnosis and preventive treatment of neurodegenerative diseases. Zh. Nevrol. Psikhiatr. im. S.S. Korsakova, 2015, vol. 115, no. 11, pp. 4–14. doi: 10.17116/jnevro20151151114-14. (In Russian)
4. Dupuis L., Loeffler J.P. Neuromuscular junction destruction during amyotrophic lateral sclerosis: Insights from transgenic models. Curr. Opin. Pharmacol., 2009, vol. 9, no. 3, pp. 341–346. doi: 10.1016/j.coph.2009.03.007.
5. Mukhamedyarov M.A., Teplov A.Y., Grishin S.N., Leushina A.V., Zefirov A.L., Palotás A. Extra-neuronal toxicity of Alzheimer's β-amyloid peptide: Comparative study on vertebrate skeletal muscles. Muscle Nerve, 2011, vol. 43, no. 6, pp. 872–877. doi: 10.1002/mus.22000.
6. Mukhamedyarov M.A., Volkov E.M., Leushina A.V., Kochunova Y.O., Palotás A., Zefirov A.L. Ionic and molecular mechanisms of β-amyloid-induced depolarization in mouse skeletal fibers. Neurosci. Behav. Physiol., 2013, vol. 43, no. 4, pp. 479–484. doi: 10.1007/s11055-013-9758-4.
7. Mukhamedyarov M.A., Volkov E.M., Khaliullina D.F., Grigoryev P.N., Zefirov A.L., Palotás A. Impaired electro-genesis in skeletal muscle fibers of transgenic Alzheimer mice. Neurochem. Int., 2014, vol. 64, pp. 24–28. doi: 10.1016/j.neuint.2013.10.014.
8. Goldman W.P., Baty J.D., Buckles V.D., Sahrmann S., Morris J.C. Motor dysfunction in mildly demented AD individuals without extrapyramidal signs. Neurology, 1999, vol. 53, no. 5, pp. 956–962. doi: 10.1212/wnl.53.5.956.
9. Wirths O., Bayer T.A. Motor impairment in Alzheimer's disease and transgenic Alzheimer's disease mouse models. Genes, Brain Behav., 2008, vol. 7, no. s1, pp. 1–5. doi: 10.1111/j.1601-183X.2007.00373.x.
10. Poehlman E.T., Dvorak R.V. Energy expenditure, energy intake, and weight loss in Alzheimer disease. Am. J. Clin. Nutr., 2000, vol. 71, no. 2, pp. 650S–655S. doi: 10.1093/ajcn/71.2.650s.
11. Lalonde R., Fukuchi K., Strazielle C. Neurologic and motor dysfunctions in APP transgenic mice. Rev. Neurosci., 2012, vol. 23, no. 4, pp. 363–379. doi: 10.1515/revneuro-2012-0041.
12. Crouch P.J., Harding S.M., White A.R., Camakaris J., Bush A.I., Masters C.L. Mechanisms of Aβ mediated neurodegeneration in Alzheimer's disease. Int. J. Biochem. Cell Biol., 2008, vol. 40, no. 2, pp. 181–198. doi: 10.1016/j.biocel.2007.07.013.
13. Querfurth H.W., LaFerla F.M. Alzheimer's disease. N. Engl. J. Med., 2010, vol. 362, no. 4, pp. 329–344.
14. Selkoe D.J., Podlisny M.B., Joachim C.L., Vickers E.A., Lee G., Fritz L.C., Oltersdorf T. Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc. Natl. Acad. Sci. USA, 1988, vol. 85, no. 19, pp. 7341–7345. doi: 10.1073/pnas.85.19.7341.
15. Mehta P.D., Pirttilä T., Mehta S.P., Sersen E.A., Aisen P.S., Wisniewski H.M. Plasma and cerebrospinal fluid levels of amyloid β proteins 1-40 and 1-42 in Alzheimer disease. Arch. Neurol., 2000, vol. 57, no. 1, pp.100–105. doi: 10.1001/archneur.57.1.100.
16. Joachim C.L., Mori H., Selkoe D.J. Amyloid β-protein deposition in tissues other than brain in Alzheimer's disease. Nature, 1989, vol. 341, no. 6239, pp. 226–230. doi: 10.1038/341226a0.
17. Soininen H., Syrjanen S., Heinonen O., Neittaanmaki H., Miettinen R., Paljarvi L., Syrjanen K., Beyreuther K., Riekkinen P. Amyloid β-protein deposition in skin of patients with dementia. Lancet, 1992, vol. 339, no. 8787, p. 245. doi: 10.1016/0140-6736(92)90046-6.
18. Rosendorff C., Beeri M.S., Silverman J.M. Cardiovascular risk factors for Alzheimer's disease. Am. J. Geriatr. Cardiol., 2007, vol. 16, no. 3, pp. 143–149. doi: 10.1111/j.1076-7460.2007.06696.x.
19. Mukhamedyarov M.A., Grishin S.N., Yusupova E.R., Zefirov A.L., Palotás A. Alzheimer's β-amyloid-induced depolarization of skeletal muscle fibers: Implications for motor dysfunctions in dementia. Cell. Physiol. Biochem., 2009, vol. 23, nos. 1–3, pp. 109–114. doi: 10.1159/000204099.
20. Mukhamedyarov M.A., Teplov A.Y., Grishin S.N., Leushina A.V., Zefirov A.L., Palotás A. Extraneuronal toxicity of Alzheimer's β-amyloid peptide: Comparative study on vertebrate skeletal muscles. Muscle Nerve, 2011, vol. 43, no. 6, pp. 872–877. doi: 10.1002/mus.22000.
21. Caccamo A., Oddo S., Sugarman M.C., Akbari Y., LaFerla F.M. Age- and region-dependent alterations in Aβ-degrading enzymes: Implications for Aβ-induced disorders. Neurobiol. Aging, 2005, vol. 26, no. 5, pp. 645–654. doi: 10.1016/j.neurobiolaging.2004.06.013.
22. Kitazawa M., Green K.N., Caccamo A., LaFerla F.M. Genetically augmenting Aβ42 levels in skeletal muscle exacerbates inclusion body myositis-like pathology and motor deficits in transgenic mice. Am. J. Pathol., 2006, vol. 168, no. 6, pp. 1986–1997. doi: 10.2353/ajpath.2006.051232.
23. Shtifman A., Ward C.W., Laver D.R., Bannister M.L., Lopez J.R., Kitazawa M., LaFerla F.M., Ikemoto N., Querfurth H.W. Amyloid-β protein impairs Ca2+ release and contractility in skeletal muscle. Neurobiol. Aging, 2010, vol. 31, no. 12, pp. 2080–2090. doi: 10.1016/j.neurobiolaging.2008.11.003.
24. Selkoe D.J. Alzheimer's disease is a synaptic failure. Science, 2002, vol. 298, no. 5594, pp. 789–791. doi: 10.1126/science.1074069.
25. Brown R.H., Al-Chalabi A. Amyotrophic lateral sclerosis. N. Engl. J. Med., 2017, vol. 377, no. 16, pp. 162–172. doi: 10.1056/NEJMra1603471.
26. Kiernan M.C., Vucic S., Cheah B.C., Turner M.R., Eisen A., Hardiman O., Burrell J.R., Zoing M.C. Amyotrophic lateral sclerosis. Lancet, 2011, vol. 377, no. 9769, pp. 942–955. doi: 10.1016/S0140-6736(10)61156-7.
27. Fischer L.R., Culver D.G., Tennant P., Davis A.A., Wang M., Castellano-Sanchez A., Khan J., Polak M.A., Glass J.D. Amyotrophic lateral sclerosis is a distal axonopathy: Evidence in mice and man. Exp. Neurol., 2004, vol. 185, no. 2, pp. 232–240. doi: 10.1016/j.expneurol.2003.10.004.
28. Rocha M.C., Pousinha P.A., Correia A.M., Sebastião A.M., Ribeiro J.A. Early changes of neuromuscular transmission in the SOD1(G93A) mice model of ALS start long before motor symptoms onset. PLoS One, 2013, vol. 8, no. 9, art. e73846, pp. 1–11. doi: 10.1371/journal.pone.0073846.
29. Rouaux C., Panteleeva I., René F., Gonzalez de Aguilar J.L., Echaniz-Laguna A., Dupuis L., Menger Y., Boutillier A.L., Loeffler J.P. Sodium valproate exerts neuroprotective effects in vivo through CREB-binding protein-dependent mechanisms but does not improve survival in an amyotrophic lateral sclerosis mouse model. J. Neurosci., 2007, vol. 27, no. 21, pp. 5535–5545. doi: 10.1523/JNEUROSCI.1139-07.2007.
30. Gould T.W., Buss R.R., Vinsant S., Prevette D., Sun W., Knudson C.M., Milligan C.E., Oppenheim R.W. Complete dissociation of motor neuron death from motor dysfunction by Bax deletion in a mouse model of ALS. J. Neurosci., 2006, vol. 26, no. 34, pp. 8774–8786. doi: 10.1523/JNEUROSCI.2315-06.2006.
31. Dewil M., dela Cruz V.F., Van Den Bosch L., Robberecht W. Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1G93A-induced motor neuron death. Neurobiol. Dis., 2007, vol. 26, no. 2, pp. 332–341. doi: 10.1016/j.nbd.2006.12.023.
32. Pramatarova A., Laganière J., Roussel J., Brisebois K., Rouleau G.A. Neuronspecific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J. Neurosci., 2001, vol. 21, no. 10, pp. 3369–3374. doi: 10.1523/JNEUROSCI.21-10-03369.2001.
33. Lino M.M., Schneider C., Caroni P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J. Neurosci., 2002, vol. 22, no. 12, pp. 4825–4832. doi: 10.1523/JNEUROSCI.22-12-04825.2002.
34. Narai H., Manabe Y., Nagai M., Nagano I., Ohta Y., Murakami T., Takehisa Y., Kamiya T., Abe K. Early detachment of neuromuscular junction proteins in ALS mice with SODG93A mutation. Neurol. Int., 2009, vol. 1, no. 1, art. e16, pp. 57–60. doi: 10.4081/ni.2009.e16.
35. Wang J., Farr G.W., Hall D.H., Li F., Furtak K., Dreier L., Horwich A.L. An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. PLoS Genet., 2009, vol. 5, no. 1, art. e1000350, pp. 1–14. doi: 10.1371/journal.pgen.1000350.
36. Maselli R.A., Wollman R.L., Leung C., Distad B., Palombi S., Richman D.P., SalazarGrueso E.F., Roos R.P. Neuromuscular transmission in amyotrophic lateral sclerosis. Muscle Nerve, 1993, vol. 16, no. 11, pp. 1193–1203. doi: 10.1002/mus.880161109.
37. Lambert E.H., Mulder D.W. Electromyographic studies in amyotrophic lateral sclerosis. Proc. Staff Meet. Mayo Clin., 1957, vol. 32, no. 17, pp. 441–446.
38. Garcia N., Santafé M.M., Tomàs M., Lanuza M.A., Tomàs J. Short-term effects of beta-amyloid25-35 peptide aggregates on transmitter release in neuromuscular synapses. J. Neuropathol. Exp. Neurol., 2008, vol. 67, no. 3, pp. 250–259. doi: 10.1097/NEN.0b013e318165e300.
39. Rozas J.L., Gomez-Sánchez L., Tomás-Zapico C., Lucas J.J., Fernández-Chacón R. Increased neurotransmitter release at the neuromuscular junction in a mouse model of polyglutamine disease. J. Neurosci., 2011, vol. 31, no. 3, pp. 1106–1113. doi: 10.1523/JNEUROSCI.2011-10.2011.
40. de Toledo Ferraz Alves T.C., Ferreira L.K., Wajngarten M., Busatto G.F. Cardiac disorders as risk factors for Alzheimer's disease. J. Alzheimer's Dis., 2010, vol. 20, no. 3, pp. 749–763. doi: 10.3233/JAD-2010-091561.
41. Dolan H., Crain B., Troncoso J., Resnick S.M., Zonderman A.B., Obrien R.J. Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of aging cohort. Ann. Neurol., 2010, vol. 68, no. 2, pp. 231–240. doi: 10.1002/ana.22055.
42. Skoog I., Lernfelt B., Landahl S., Palmertz B., Andreasson L.A., Nilsson L., Persson G., Odén A., Svanborg A. 15-year longitudinal study of blood pressure and dementia. Lancet, 1996, vol. 347, no. 9009, pp. 1141–1145. doi: 10.1016/s0140-6736(96)90608-x.
43. Palotás A., Reis H.J., Bogáts G., Babik B., Racsmány M., Engvau L., Kecskeméti E., Juhász A., Vieira L.B., Teixeira A.L., Mukhamedyarovi M.A., Rizvanov A.A., Yalvaç M.E., Guimarães M.M., Ferreira C.N., Zefirov A.L., Kiyasov A.P., Wang L., Janka Z., Kálmán J. Coronary artery bypass surgery provokes Alzheimer's disease-like changes in the cerebrospinal fluid. J. Alzheimer's Dis., 2010, vol. 21, no. 4, pp. 1153–1164. doi: 10.3233/jad-2010-100702.
44. Reis H.J., Wang L., Verano-Braga T., Pimenta A.M., Kálmán J., Bogáts G., Babik B., Vieira L.B., Teixeira A.L., Mukhamedyarov M.A., Zefirov A.L., Kiyasov A.P., Rizvanov A.A., Matin K., Palotás M., Guimarães M.M., Ferreira C.N., Yalvaç M.E., Janka Z., Palotás A. Evaluation of post-surgical cognitive function and protein fingerprints in the cerebro-spinal fluid utilizing surface-enhanced laser Desorption/Ionization time-offlight mass-spectrometry (SELDI-TOF MS) after coronary artery bypass grafting: Review of proteomic analytic tools and introducing a new syndrome. Curr. Med. Chem., 2011, vol. 18, no. 7, pp. 1019–1037. doi: 10.2174/092986711794940897.
45. Love S., Miners S., Palmer J., Chalmers K., Kehoe P. Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy. Front. Biosci., 2009, vol. 14, pp. 4778–4792. doi: 10.2741/3567.
46. Tian J., Shi J., Mann D.M. Cerebral amyloid angiopathy and dementia. Panminerva Med., 2004, vol. 46, no. 4, pp. 253–264.
47. Van Nostrand W.E., Melchor J.P., Ruffini L. Pathologic amyloid ß-protein cell surface fibril assembly on cultured human cerebrovascular smooth muscle cells. J. Neurochem., 1998, vol. 70, no. 1, pp. 216–223. doi: 10.1046/j.1471-4159.1998.70010216.x.
48. Paris D., Patel N., DelleDonne A., Quadros A., Smeed R., Mullan M. Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis. Neurosci. Lett., 2004, vol. 366, no. 1, pp. 80–85. doi: 10.1016/j.neulet.2004.05.017.
49. Paris D., Humphrey J., Quadros A., Patel N., Crescentini R., Crawford F., Mullan M. Vasoactive effects of Aß in isolated human cerebrovessels and in a transgenic mouse model of Alzheimer's disease: Role of inflammation. Neurol. Res., 2003, vol. 25, no. 6, pp. 642–651. doi: 10.1179/016164103101201940.
50. Leushina A.V., Gaifullina R.F., Zefirov A.L., Palotás A., Mukhamedyarov M.A. Cellular and receptor mechanisms of impairment of myocardium and aorta contractility at Alzheimer's disease model. Cell. Transplant. Tissue Eng., 2012, vol. 7, no. 3, pp. 98–100.
51. Zamolodchikov D., Strickland S. Aß delays fibrin clot lysis by altering fibrin structure and attenuating plasminogen binding to fibrin. Blood, 2012, vol. 119, no. 14, pp. 3342–3351. doi: 10.1182/blood-2011-11-389668.
52. Sparks D.L., Liu H., Scheff S.W., Coyne C.M., Hunsaker J.C., 3rd. Temporal sequence of plaque formation in the cerebral cortex of non-demented individuals. J. Neuropathol. Exp. Neurol., 1993, vol. 52, no. 2, pp. 135–142. doi: 10.1097/00005072-199303000-00006.
53. Strittmatter W.J., Saunders A.M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G.S., Roses A.D. Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA, 1993, vol. 90, no. 5, pp. 1977–1981. doi: 10.1073/pnas.90.5.1977.
54. Hofman A., Ott A., Breteler M.M., Bots M.L., Slooter A.J., van Harskamp F., van Duijn C.N., Van Broeckhoven C., Grobbee D.E. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet, 1997, vol. 349, no. 9046, pp. 151–154. doi: 10.1016/S0140-6736(96)09328-2.
55. Stewart R., Prince M., Mann A. Vascular risk factors and Alzheimer's disease. Aust. N. Z. J. Psychiatry, 1999, vol. 33, no. 6, pp. 809–813. doi: 10.1046/j.1440-1614.1999.00657.x.
56. Schmidt R., Schmidt H., Fazekas F. Vascular risk factors in dementia. J. Neurol., 2000, vol. 247, no. 2, pp. 81–87. doi: 10.1007/s004150050021.
57. Shi J., Perry G., Smith M.A., Friedland R.P. Vascular abnormalities: The insidious pathogenesis of Alzheimer's disease. Neurobiol. Aging, 2000, vol. 21, no. 2, pp. 357–361. doi: 10.1016/s0197-4580(00)00119-6.
58. Turdi S., Guo R., Huff A.F., Wolf E.M., Culver B., Ren J. Cardiomyocyte contractile dysfunction in the APPswe/PS1dE9 mouse model of Alzheimer's disease. PLoS One, 2009, vol. 4, no. 6, art. e6033, pp. 1–12. doi: 10.1371/journal.pone.0006033.
59. Asai H., Hirano M., Udaka F., Shimada K., Oda M., Kubori T., Nishinaka K., Tsujimura T., Izumi Y., Konishi N., Matsumoto S., Kameyama M., Ueno S. Sympathetic disturbances increase risk of sudden cardiac arrest in sporadic ALS. J. Neurol. Sci., 2007, vol. 254, nos. 1–2, pp. 78–83. doi: 10.1016/j.jns.2007.01.007.
60. Druschky A., Spitzer A., Platsch G., Claus D., Feistel H., Druschky K., Hilz M.J., Neundorfer B. Cardiac sympathetic denervation in early stages of amyotrophic lateral sclerosis demonstrated by 123I-MIBG-SPECT. Acta Neurol. Scand., 1999, vol. 99, no. 5, pp. 308–314. doi: 10.1111/j.1600-0404.1999.tb00681.x.
61. Kehoe P., Krawczak M., Harper P.S., Owen M.J., Jones A.L. Age of onset in Huntington disease: Sex specific influence of apolipoprotein E genotype and normal CAG repeat length. J. Med. Genet., 1999, vol. 36, no. 2, pp. 108–111. doi: 10.1136/jmg.36.2.108.
62. Kieburtz K., MacDonald M., Shih C., Feigin A., Steinberg K., Bordwell K., Zimmerman C., Srinidhi J., Sotack J., Gusella J., Shoulson I. Trinucleotide repeat length and progression of illness in Huntington's disease. J. Med. Genet., 1994, vol. 31, no. 11, pp. 872–874. doi: 10.1136/jmg.31.11.872.
63. Mihm M.J., Amann D.M., Schanbacher B.L., Altschuld R.A., Bauer J.A., Hoyt K.R. Cardiac dysfunction in the R6/2 mouse model of Huntington's disease. Neurobiol. Dis., 2007, vol. 25, no. 2, pp. 297–308. doi: 10.1016/j.nbd.2006.09.016.
64. Sassone J., Colciago C., Cislaghi G., Silani V., Ciammola A. Huntington's disease: The current state of research with peripheral tissues. Exp. Neurol., 2009, vol. 219, no. 2, pp. 385–397. doi: 10.1016/j.expneurol.2009.05.012.
Received
July 27, 2018
Mukhamedyarov Marat Alexandrovich, Doctor of Medical Sciences, Professor of Department of Physiology
Kazan State Medical University
ul. Butlerova, 49, Kazan, 420012 Russia
E-mail: maratm80@list.ru
Petukhova Elena Olegovna, Researcher of Institute of Neuroscience
Kazan State Medical University
ul. Butlerova, 49, Kazan, 420012 Russia
Ushanova Elmira Asgatovna, Junior Researcher of Institute of Neuroscience, PhD Student of Department of Human Health Protection
Kazan State Medical University
ul. Butlerova, 49, Kazan, 420012 Russia
Kazan Federal University
ul. Kremlevskaya, 18, Kazan, 420008 Russia
Nurkhametova Dilyara Farkhadovna, Junior Researcher of OpenLab Laboratory of Neurobiology
Kazan Federal University
ul. Kremlevskaya, 18, Kazan, 420008 Russia
Leushina Alina Vladimirovna, Junior Researcher of Institute of Neuroscience
Kazan State Medical University
ul. Butlerova, 49, Kazan, 420012 Russia
Palotás Andras, PhD, Director
Private Medical Practice and Research Center “Asklepios-Med”
Kossuth Lajos sgt. 23, Szeged, H-6722 Hungary
Zefirov Andrey Lvovich, Corresponding Member of Russian Academy of Sciences, Doctor of Medical Sciences, Head of Department of Physiology
Kazan State Medical University
ul. Butlerova, 49, Kazan, 420012 Russia
For citation: Mukhamedyarov M.A., Petukhova E.O., Ushanova E.A., Nurkhametova D.F., Leushina A.V., Palotás A., Zefirov A.L. Peripheral dysfunctions in neurodegenerative diseases: Mechanisms and contribution to pathogenesis. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2018, vol. 160, no. 4, pp. 663–676.
Для цитирования: Mukhamedyarov M.A., Petukhova E.O., Ushanova E.A., Nurkhametova D.F., Leushina A.V., Palotás A., Zefirov A.L. Peripheral dysfunctions in neurodegenerative diseases: Mechanisms and contribution to pathogenesis // Учен. зап. Казан. ун-та. Сер. Естеств. науки. – 2018. – Т. 160, кн. 4. – С. 663–676.
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