Abstrakt

Choroby neurodegeneracyjne są istotnym problemem medycznym i społecznym wśród osób starszych, których odsetek znacząco wzrasta w większości krajów na świecie. Ich przyczyną jest dysfunkcja i niszczenie neuronów spowodowane proteinopatiami, które prowadzą do tworzenia się patologicznych złogów w neuronach, komórkach glejowych oraz w przestrzeni międzykomórkowej. Do białek, których cząsteczki łatwo się destabilizują w wyniku mutacji punktowych lub endogennych procesów należą alfa-synukleina (ASN), białko tau oraz TDP- 43. Patologiczne postaci tych białek tworzą charakterystyczne dla każdego z nich agregaty, które kumulują się w neuronach i są przyczyną różnych postaci chorób otępiennych i zaburzeń motorycznych. Najczęstszymi przyczynami zespołów otępiennych są tauopatie. Do tauopatii pierwotnych należą: postępujące porażenie nadjądrowe (PSP), zwyrodnienie korowo- -podstawne (CBD), choroba Picka (PiD) oraz otępienie czołowo-skroniowe (FTD), w których zmodyfikowane cząsteczki tau zaburzają transport aksonalny przez mikrotubule prowadząc do nieprawidłowej dystrybucji białek w neuronach, a helikalne fragmenty i splątki białka degradują neurony w różnych strukturach mózgu. Do tauopatii mieszanych zalicza się chorobę Alzheimera, w której za degenerację hipokampa, kory śródwęchowej oraz jąder migdałowatych odpowiadają splątki hiperfosforylowanego tau wraz ze złogami amyloidu β. Do synukleinopatii należy choroba Parkinsona, zanik wieloukładowy (MSA) oraz otępienie z ciałami Lewy’ego, w których dochodzi do degeneracji neuronów szlaków pozapiramidowych lub tak jak w MSA, także nerwów autonomicznych. Inkluzje rybonukleoproteiny TDP-43 w cytoplazmie są przyczyną degeneracji neuronów ruchowych w stwardnieniu zanikowym bocznym (ALS), a także w jednym z wariantów otępienia czołowo-skroniowego (FTLD-TDP). Opracowanie poświęcone jest budowie białek ASN, tau i TDP-43 oraz genetycznym i sporadycznym przyczynom destabilizacji cząsteczek, ich agregacji i nieprawidłowego rozmieszczenia w neuronach prowadzących do neurodegeneracji.

Przypisy

• 1. Abner E.L., Kryscio R.J., Schmitt F.A., Santacruz K.S., Jicha G.A., LinY., Neltner J.M., Smith C.D., Van Eldik L.J., Nelson P.T.: “End-stage” neurofibrillarytangle pathology in preclinical Alzheimer’s disease: Fact orfiction? J. Alzheimers Dis., 2011; 25: 445 –453
  Google Scholar
• 2. Ahmed T., Van der Jeugd A., Blum D., Galas M.C., D’Hooge R., BueeL., Balschun D.: Cognition and hippocampal synaptic plasticity in micewith a homozygous tau deletion. Neurobiol. Aging, 2014; 35: 2474 –2478
  Google Scholar
• 3. Amadoro G., Corsetti V., Ciotti M.T., Florenzano F., Capsoni S., AmatoG., Calissano P.: Endogenous Aβ causes cell death via early tau hyperphosphorylation.Neurobiol. Aging, 2011; 32: 969 –990
  Google Scholar
• 4. An W.L., Cowburn R.F., Li L., Braak H., Alafuzoff I., Iqbal K., Iqbal I.G.,Winblad B., Pei J.J.: Up-regulation of phosphorylated/activated p70 S6kinase and its relationship to neurofibrillary pathology in Alzheimer’sdisease. Am. J. Pathol., 2003; 163: 591 –607
  Google Scholar
• 5. Arun P., Oguntayo S., Albert S.V., Gist I., Wang Y., Nambiar M.P., LongJ.B.: Acute decrease in alkaline phosphatase after brain injury: A potentialmechanism for tauopathy. Neurosci. Lett., 2015; 609: 152 –158
  Google Scholar
• 6. Avila J., Jiménez J.S., Sayas C.L., Bolós M., Zabala J.C., Rivas G., HernándezF.: Tau structures. Front. Aging Neurosci., 2016; 8: 262
  Google Scholar
• 7. Ayala Y.M., Zago P., D’Ambrogio A., Xu Y.F., Petrucelli L., Buratti E.,Baralle F.E.: Structural determinants of the cellular localization andshuttling of TDP-43. J. Cell Sci., 2008; 121: 3778–3785
  Google Scholar
• 8. Bartels T., Choi J.G., Selkoe D.J.: α-Synuclein occurs physiologicallyas a helically folded tetramer that resists aggregation. Nature, 2011;477: 107 –110
  Google Scholar
• 9. Berning B.A., Walker A.K.: The pathobiology of TDP-43 C-terminalfragments in ALS and FTLD. Front. Neurosci., 2019; 13: 335
  Google Scholar
• 10. Brandt R., Léger J., Lee G.: Interaction of tau with the neural plasmamembrane mediated by tau’s amino-terminal projection domain. J. CellBiol., 1995; 131: 1327 –1340
  Google Scholar
• 11. Burré J., Sharma M., Südhof T.C.: α-Synuclein assembles into higherordermultimers upon membrane binding to promote SNARE complexformation. Proc. Natl. Acad. Sci. USA, 2014; 111: E4274–E4283
  Google Scholar
• 12. Bussell R.Jr., Eliezer D.: Effects of Parkinson’s disease-linked mutationson the structure of lipid-associated α-synuclein. Biochemistry,2004; 43: 4810–4818
  Google Scholar
• 13. Chartier-Harlin M.C., Kachergus J., Roumier C., Mouroux V., DouayX., Lincoln S., Levecque C., Larvor L., Andrieux J., Hulihan M., WaucquierN., Defebvre L., Amouyel P., Farrer M., Destée A.: α-synucleinlocus duplication as a cause of familial Parkinson’s disease. Lancet,2004; 364: 1167–1169
  Google Scholar
• 14. Chen R.H., Wislet-Gendebien S., Samuel F., Visanji N.P., Zhang G.,Marsilio D., Langman T., Fraser P.E., Tandon A.: α-Synuclein membraneassociation is regulated by the Rab3a recycling machinery and presynapticactivity. J. Biol. Chem., 2013; 288: 7438 –7449
  Google Scholar
• 15. Cherry J.D., Tripodis Y., Alvarez V.E., Huber B., Kiernan P.T., DaneshvarD.H., Mez J., Montenigro P.H., Solomon T.M., Alosco M.L., Stern R.A.,McKee A.C., Stein T.D.: Microglial neuroinflammation contributes to tauaccumulation in chronic traumatic encephalopathy. Acta Neuropathol.Commun., 2016; 4: 112
  Google Scholar
• 16. Chiang C.H., Grauffel C., Wu L.S., Kuo P.H., Doudeva L.G., Lim C., ShenC.K., Yuan H.S.: Structural analysis of disease-related TDP-43 D169Gmutation: Linking enhanced stability and caspase cleavage efficiencyto protein accumulation. Sci. Rep., 2016; 6: 21581
  Google Scholar
• 17. Choi B.K., Choi M.G., Kim J.Y., Yang Y., Lai Y., Kweon D.H., Lee N.K.,Shin Y.K.: Large α-synuclein oligomers inhibit neuronal SNARE-mediatedvesicle docking. Proc. Natl. Acad. Sci. USA, 2013; 110: 4087 –4092
  Google Scholar
• 18. Clavaguera F., Bolmont T., Crowther R.A., Abramowski D., Frank S.,Probst A., Fraser G., Stalder A.K., Beibel M., Staufenbiel M., Jucker M.,Goedert M., Tolnay M.: Transmission and spreading of tauopathy intransgenic mouse brain. Nat. Cell Biol., 2009; 11: 909 –913
  Google Scholar
• 19. Cohen T.J., Hwang A.W., Restrepo C.R., Yuan C.X., Trojanowski J.Q.,Lee V.M.: An acetylation switch controls TDP-43 function and aggregationpropensity. Nat. Commun., 2015; 6: 5845
  Google Scholar
• 20. Conway K.A., Harper J.D., Lansbury P.T.: Accelerated in vitro fibrilformation by a mutant α-synuclein linked to early-onset Parkinsondisease. Nat. Med., 1998; 4: 1318 –1320
  Google Scholar
• 21. Coskuner O., Wise-Scira O.: Structures and free energy landscapes ofthe A53T mutant-type α-synuclein protein and impact of A53T mutationon the structures of the wild-type α-synuclein protein with dynamics.ACS Chem. Neurosci., 2013; 4: 1101 –1113
  Google Scholar
• 22. Dawson H.N., Ferreira A., Eyster M.V., Ghoshal N., Binder L.I., VitekM.P.: Inhibition of neuronal maturation in primary hippocampal neuronsfrom tau deficient mice. J. Cell Sci., 2001; 114: 1179 –1187
  Google Scholar
• 23. Dayanandan R., Van Slegtenhorst M., Mack T.G., Ko L., Yen S.H.,Leroy K., Brion J.P., Anderton B.H., Hutton M., Lovestone S.: Mutationsin tau reduce its microtubule binding properties in intact cells andaffect its phosphorylation. FEBS Lett., 1999; 446: 228 –232
  Google Scholar
• 24. Dementia. https://www.who.int/en/news-room/fact-sheets/detail/dementia (17.04.2020)
  Google Scholar
• 25. Derisbourg M., Leghay C., Chiappetta G., Fernandez-Gomez F.J.,Laurent C., Demeyer D., Carrier S., Buée-Scherrer V., Blum D., Vinh J.,Sergeant N., Verdier Y., Buée L., Hamdane M.: Role of the Tau N-terminalregion in microtubule stabilization revealed by new endogenoustruncated forms. Sci. Rep., 2015; 5: 9659
  Google Scholar
• 26. Derkinderen P., Scales T.M., Hanger D.P., Leung K.Y., Byers H.L.,Ward M.A., Lenz C., Price C., Bird I.N., Perera T., Kellie S., Williamson R.,Noble W., Van Etten R.A., Leroy K. i wsp.: Tyrosine 394 is phosphorylatedin Alzheimer’s paired helical filament tau and in fetal tau with c-Abl as the candidate tyrosine kinase. J. Neurosci., 2005; 25: 6584 –6593
  Google Scholar
• 27. Dixit R., Ross J.L., Goldman Y.E., Holzbaur E.L.: Differential regulationof dynein and kinesin motor proteins by tau. Science, 2008;319: 1086 –1089
  Google Scholar
• 28. Doherty C.P.A., Ulamec S.M., Maya-Martinez R., Good S.C.,Makepeace J., Khan G.N., van Oosten-Hawle P., Radford S.E., BrockwellD.J.: A short motif in the N-terminal region of α-synuclein iscritical for both aggregation and function. Nat. Struct. Mol. Biol.,2020; 27: 249 –259
  Google Scholar
• 29. Dugger B.N., Dickson D.W.: Pathology of neurodegenerative diseases.Cold Spring Harb. Perspect. Biol., 2017; 9: a028035
  Google Scholar
• 30. Fares M.B., Ait-Bouziad N., Dikiy I., Mbefo M.K., Jovičić A., Kiely A.,Holton J.L., Lee S.J., Gitler A.D., Eliezer D., Lashuel H.A.: The novel Parkinson’sdisease linked mutation G51D attenuates in vitro aggregationand membrane binding of α-synuclein, and enhances its secretion andnuclear localization in cells. Hum. Mol. Genet., 2014; 23: 4491 –4509
  Google Scholar
• 31. Fischer D., Mukrasch M.D., Biernat J., Bibow S., Blackledge M.,Griesinger C., Mandelkow E., Zweckstetter M.: Conformational changesspecific for pseudophosphorylation at serine 262 selectively impairbinding of tau to microtubules. Biochemistry, 2009; 48: 10047 –10055
  Google Scholar
• 32. Flores B.N., Li X., Malik A.M., Martinez J., Beg A.A., Barmada S.J.:An intramolecular salt bridge linking TDP43 RNA binding, proteinstability, and TDP43-dependent neurodegeneration. Cell. Rep., 2019;27: 1133 –1150.e8
  Google Scholar
• 33. François-Moutal L., Perez-Miller S., Scott D.D., Miranda V.G., MollasalehiN., Khanna M.: Structural insights into TDP-43 and effects ofpost-translational modifications. Front. Mol. Neurosci., 2019; 12: 301
  Google Scholar
• 34. Fraser P.E., Yang D.S., Yu G., Lévesque L., Nishimura M., ArawakaS., Serpell L.C., Rogaeva E., St George-Hyslop P.: Presenilin structure,function and role in Alzheimer disease. Biochim. Biophys. Acta, 2000;1502: 1–15
  Google Scholar
• 35. Frenkel-Pinter M., Stempler S., Tal-Mazaki S., Losev Y., Singh-Anand A., Escobar-Álvarez D., Lezmy J., Gazit E., Ruppin E., Segal D.:Altered protein glycosylation predicts Alzheimer’s disease and modulatesits pathology in disease model Drosophila. Neurobiol. Aging,2017; 56: 159 –171
  Google Scholar
• 36. Fusco G., Chen S.W., Williamson P.T.F., Cascella R., Perni M., JarvisJ.A., Cecchi C., Vendruscolo M., Chiti F., Cremades N., Ying L., DobsonC.M., De Simone A.: Structural basis of membrane disruption and cellulartoxicity by α-synuclein oligomers. Science, 2017; 358: 1440 –1443
  Google Scholar
• 37. Gámez-Valero A., Beyer K.: Alternative Splicing of alpha- andbeta-synuclein genes plays differential roles in synucleinopathies.Genes, 2018; 9: 63
  Google Scholar
• 38. Garnier C., Devred F., Byrne D., Puppo R., Roman A.Y., MalesinskiS., Golovin A.V., Lebrun R., Ninkina N.N., Tsvetkov P.O.: Zinc binding toRNA recognition motif of TDP-43 induces the formation of amyloidlikeaggregates. Sci. Rep., 2017; 7: 6812
  Google Scholar
• 39. Gauthier-Kemper A., Suárez Alonso M., Sündermann F., NiewidokB., Fernandez M.P., Bakota L., Heinisch J.J., Brandt R.: Annexins A2 andA6 interact with the extreme N terminus of tau and thereby contributeto tau’s axonal localization. J. Biol. Chem., 2018; 293: 8065 –8076
  Google Scholar
• 40. Gong C.X., Singh T.J., Grundke-Iqbal I., Iqbal K.: Phosphoproteinphosphatase activities in Alzheimer disease brain. J. Neurochem.,1993; 61: 921 –927
  Google Scholar
• 41. Götz J., Probst A., Spillantini M.G., Schäfer T., Jakes R., Bürki K.,Goedert M.: Somatodendritic localization and hyperphosphorylationof tau protein in transgenic mice expressing the longest human braintau isoform. EMBO J., 1995; 14: 1304 –1313
  Google Scholar
• 42. Gómez-Santos C., Ferrer I., Reiriz J., Viñals F., Barrachina M., AmbrosioS.: MPP+ increases alpha-synuclein expression and ERK/MAPkinasephosphorylation in human neuroblastoma SH-SY5Y cells. BrainRes., 2002; 935: 32 –39
  Google Scholar
• 43. Hans F., Eckert M., von Zweydorf F., Gloeckner C.J., Kahle P.J.:Identification and characterization of ubiquitinylation sites in TARDNA-binding protein of 43 kDa (TDP-43). J. Biol. Chem., 2018; 293: 16083 –16099
  Google Scholar
• 44. Heicklen-Klein A., Ginzburg I.: Tau promoter confers neuronalspecificity and binds Sp1 and AP-2. J. Neurochem., 2000; 75: 1408 –1418
  Google Scholar
• 45. Highley J.R., Kirby J., Jansweijer J.A., Webb P.S., HewamaddumaC.A., Heath P.R., Higginbottom A., Raman R., Ferraiuolo L., Cooper-Knock J., McDermott C.J., Wharton S.B., Shaw P.J., Ince P.G.: Loss ofnuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes alteredexpression of splicing machinery and widespread dysregulation ofRNA splicing in motor neurones. Neuropathol. Appl. Neurobiol., 2014;40: 670 –685
  Google Scholar
• 46. Hirokawa N., Shiomura Y., Okabe S.: Tau proteins: the molecularstructure and mode of binding on microtubules. J. Cell Biol., 1988;107: 1449–1459
  Google Scholar
• 47. Hosokawa M., Kondo H., Serrano G.E., Beach T.G., Robinson A.C.,Mann D.M., Akiyama H., Hasegawa M., Arai T.: Accumulation of multipleneurodegenerative disease-related proteins in familial frontotemporallobar degeneration associated with granulin mutation. Sci.Rep., 2017; 7: 1513
  Google Scholar
• 48. Huin V., Buée L., Behal H., Labreuche J., Sablonnière B., DhaenensC.M.: Alternative promoter usage generates novel shorter MAPTmRNA transcripts in Alzheimer’s disease and progressive supranuclearpalsy brains. Sci. Rep., 2017; 7: 12589
  Google Scholar
• 49. Iguchi Y., Katsuno M., Ikenaka K., Ishigaki S., Sobue G.: Amyotrophiclateral sclerosis: An update on recent genetic insights. J Neurol.,2013; 260: 2917 –2927
  Google Scholar
• 50. Ittner L.M., Götz J.: Amyloid-β and tau – a toxic pas de deux inAlzheimer’s disease. Nat. Rev. Neurosci., 2011; 12: 65 –72
  Google Scholar
• 51. Ittner L.M., Ke Y.D., Delerue F., Bi M., Gladbach A., van Eersel J.,Wölfing H., Chieng B.C., Christie M.J., Napier I.A., Eckert A., Staufenbiel M., Hardeman E., Götz J.: Dendritic function of tau mediates amyloid-βtoxicity in Alzheimer’s disease mouse models. Cell, 2010; 142: 387 –397
  Google Scholar
• 52. Jakes R., Spillantini M.G., Goedert M.: Identification of two distinctsynucleins from human brain. FEBS Lett., 1994; 345: 27 –32
  Google Scholar
• 53. Jao C.C., Der-Sarkissian A., Chen J., Langen R.: Structure of membrane-bound alpha-synuclein studied by site-directed spin labeling.Proc. Natl. Acad. Sci. USA, 2004; 101: 8331 –8336
  Google Scholar
• 54. Jiang L.L., Xue W., Hong J.Y., Zhang J.T., Li M.J., Yu S.N., He J.H.,Hu H.Y.: The N-terminal dimerization is required for TDP-43 splicingactivity. Sci. Rep., 2017; 7: 6196
  Google Scholar
• 55. Jin H., Kanthasamy A., Ghosh A., Yang Y., Anantharam V., KanthasamyA.G.: α-Synuclein negatively regulates protein kinase Cδ expressionto suppress apoptosis in dopaminergic neurons by reducingp300 histone acetyltransferase activity. J. Neurosci., 2011; 31: 2035 –2051
  Google Scholar
• 56. Johnson G.V., Seubert P., Cox T.M., Motter R., Brown J.P., GalaskoD.: The tau protein in human cerebrospinal fluid in Alzheimer’s diseaseconsists of proteolytically derived fragments. J. Neurochem., 1997; 68: 430 –433
  Google Scholar
• 57. Kametani F., Nonaka T., Suzuki T., Arai T., Dohmae N., Akiyama H.,Hasegawa M.: Identification of casein kinase-1 phosphorylation sites onTDP-43. Biochem. Biophys. Res. Commun., 2009; 382: 405 –409
  Google Scholar
• 58. Kanaan N.M., Morfini G.A., LaPointe N.E., Pigino G.F., Patterson K.R.,Song Y., Andreadis A., Fu Y., Brady S.T., Binder L.I.: Pathogenic forms oftau inhibit kinesin-dependent axonal transport through a mechanisminvolving activation of axonal phosphotransferases. J. Neurosci., 2011;31: 9858 –9868
  Google Scholar
• 59. Kawahara M., Ohtsuka I., Yokoyama S., Kato-Negishi M., SadakaneY.: Membrane incorporation, channel formation, and disruption of calciumhomeostasis by Alzheimer’s β-amyloid protein. Int. J. AlzheimersDis., 2011; 2011: 304583
  Google Scholar
• 60. Kenessey A., Nacharaju P., Ko L.W., Yen S.H.: Degradation of tau bylysosomal enzyme cathepsin D: Implication for Alzheimer neurofibrillarydegeneration. J. Neurochem., 1997; 69: 2026 –2038
  Google Scholar
• 61. Khalaf O., Fauvet B., Oueslati A., Dikiy I., Mahul-Mellier A.L., RuggeriF.S., Mbefo M.K., Vercruysse F., Dietler G., Lee S.J., Eliezer D., LashuelH.A.: The H50Q mutation enhances α-synuclein aggregation, secretion,and toxicity. J. Biol. Chem., 2014; 289: 21856 –21876
  Google Scholar
• 62. Kosik K.S., Orecchio L.D., Bakalis S., Neve R.L.: Developmentally regulatedexpression of specific tau sequences. Neuron, 1989; 2: 1389 –1397
  Google Scholar
• 63. Kühnlein P., Sperfeld A.D., Vanmassenhove B., Van Deerlin V., LeeV.M., Trojanowski J.Q., Kretzschmar H.A., Ludolph A.C., Neumann M.:Two German kindreds with familial amyotrophic lateral sclerosis dueto TARDBP mutations. Arch. Neurol., 2008; 65: 1185 –1189
  Google Scholar
• 64. Kumar S., Jangir D.K., Kumar R., Kumari M., Bhavesh N.S., MaitiT.K.: Role of sporadic Parkinson disease associated mutations A18Tand A29S in enhanced α-synuclein fibrillation and cytotoxicity. ACSChem. Neurosci., 2018; 9: 230 –240
  Google Scholar
• 65. Lei P., Ayton S., Finkelstein D.I., Spoerri L., Ciccotosto G.D., WrightD.K., Wong B.X., Adlard P.A., Cherny R.A., Lam L.Q., Roberts B.R., VolitakisI., Egan G.F., McLean C.A., Cappai R. i wsp.: Tau deficiency inducesparkinsonism with dementia by impairing APP-mediated iron export.Nat. Med., 2012; 18: 291 –295
  Google Scholar
• 66. Liu F., Grundke-Iqbal I., Iqbal K., Gong C.X.: Contributions of proteinphosphatases PP1, PP2A, PP2B and PP5 to the regulation of tauphosphorylation. Eur. J. Neurosci., 2005; 22: 1942 –1950
  Google Scholar
• 67. Liu Y., Lv K., Li Z., Yu A.C., Chen J., Teng J.: PACSIN1, a Tau-interactingprotein, regulates axonal elongation and branching by facilitatingmicrotubule instability. J. Biol. Chem., 2012; 287: 39911 –39924
  Google Scholar
• 68. Lu J., Duan W., Guo Y., Jiang H., Li Z., Huang J., Hong K., Li C.: Mitochondrialdysfunction in human TDP-43 transfected NSC34 celllines and the protective effect of dimethoxy curcumin. Brain Res.Bull., 2012; 89: 185 –190
  Google Scholar
• 69. Lundblad M., Decressac M., Mattsson B., Björklund A.: Impairedneurotransmission caused by overexpression of α-synuclein in nigraldopamine neurons. Proc. Natl. Acad. Sci. USA, 2012; 109: 3213 –3219
  Google Scholar
• 70. Maroteaux L., Campanelli J.T., Scheller R.H.: Synuclein: A neuronspecificprotein localized to the nucleus and presynaptic nerve terminal.J. Neurosci., 1988; 8: 2804 –2815
  Google Scholar
• 71. Martin L., Latypova X., Terro F.: Post-translational modificationsof tau protein: Implications for Alzheimer’s disease. Neurochem. Int.,2011; 58: 458 –471
  Google Scholar
• 72. Matsuoka Y., Picciano M., Malester B., LaFrancois J., Zehr C., DaeschnerJ.M., Olschowka J.A., Fonseca M.I., O’Banion M.K., Tenner A.J.,Lemere C.A., Duff K.: Inflammatory responses to amyloidosis in atransgenic mouse model of Alzheimer’s disease. Am. J. Pathol., 2001;158: 1345 –1354
  Google Scholar
• 73. Meade R.M., Fairlie D.P., Mason J.M.: Alpha-synuclein structureand Parkinson’s disease – lessons and emerging principles. Mol. Neurodegener.,2019; 14: 29
  Google Scholar
• 74. Mena R., Luna-Muñoz J.C.: Stages of pathological tau-proteinprocessing in Alzheimer’s disease: From soluble aggregations to polymerizationinto insoluble Tau-PHFs. W: Current Hypotheses andResearch Milestones in Alzheimer’s Disease, red.: R.B. Maccoini, G.Perry. Springer US, New York 2009, 79 –91
  Google Scholar
• 75. Min S.W., Cho S.H., Zhou Y., Schroeder S., Haroutunian V., SeeleyW.W., Huang E.J., Shen Y., Masliah E., Mukherjee C., Meyers D., ColeP.A., Ott M., Gan L.: Acetylation of tau inhibits its degradation andcontributes to tauopathy. Neuron, 2010; 67: 953 –966
  Google Scholar
• 76. Mohite G.M., Navalkar A., Kumar R., Mehra S., Das S., Gadhe L.G.,Ghosh D., Alias B., Chandrawanshi V., Ramakrishnan A., Mehra S., MajiS.K.: The familial α-synuclein A53E mutation enhances cell death inresponse to environmental toxins due to a larger population of oligomers.Biochemistry, 2018; 57: 5014 –5028
  Google Scholar
• 77. Neumann M., Kwong L.K., Lee E.B., Kremmer E., Flatley A., Xu Y.,Forman M.S., Troost D., Kretzschmar H.A., Trojanowski J.Q., Lee V.M.:Phosphorylation of S409/410 of TDP-43 is a consistent feature in allsporadic and familial forms of TDP-43 proteinopathies. Acta Neuropathol.,2009; 117: 137 –149
  Google Scholar
• 78. Neumann M., Sampathu D.M., Kwong L.K., Truax A.C., MicsenyiM.C., Chou T.T., Bruce J., Schuck T., Grossman M., Clark C.M., McCluskeyL.F., Miller B.L., Masliah E., Mackenzie I.R., Feldman H. i wsp.: UbiquitinatedTDP-43 in frontotemporal lobar degeneration and amyotrophiclateral sclerosis. Science, 2006; 314: 130 –133
  Google Scholar
• 79. Neve R.L., Harris P., Kosik K.S., Kurnit D.M., Donlon T.A.: Identificationof cDNA clones for the human microtubule-associated protein tauand chromosomal localization of the genes for tau and microtubuleassociatedprotein 2. Brain. Res., 1986; 387: 271 –280
  Google Scholar
• 80. Ou S.H., Wu F., Harrich D., García-Martínez L.F., Gaynor R.B.: Cloningand characterization of a novel cellular protein, TDP-43, that bindsto human immunodeficiency virus type 1 TAR DNA sequence motifs.J. Virol., 1995; 69: 3584 –3596
  Google Scholar
• 81. Ozer R.S., Halpain S.: Phosphorylation-dependent localization ofmicrotubule-associated protein MAP2c to the actin cytoskeleton. Mol.Biol. Cell, 2000; 11: 3573 –3587
  Google Scholar
• 82. Pandey N., Schmidt R.E., Galvin J.E.: The alpha-synuclein mutationE46K promotes aggregation in cultured cells. Exp. Neurol., 2006;197: 515 –520
  Google Scholar
• 83. Pesiridis G.S., Lee V.M., Trojanowski J.Q.: Mutations in TDP-43 linkglycine-rich domain functions to amyotrophic lateral sclerosis. Hum.Mol. Genet., 2009; 18: R156 –R162
  Google Scholar
• 84. Pinarbasi E.S., Cağatay T., Fung H.Y.J., Li Y.C., Chook Y.M., ThomasP.J.: Active nuclear import and passive nuclear export are the primarydeterminants of TDP-43 localization. Sci. Rep., 2018; 8: 7083
  Google Scholar
• 85. Plotegher N., Kumar D., Tessari I., Brucale M., Munari F., TosattoL., Belluzzi E., Greggio E., Bisaglia M., Capaldi S., Aioanei D., MammiS., Monaco H.L., Samo B., Bubacco L.: The chaperone-like protein 14-3-3η interacts with human α-synuclein aggregation intermediatesrerouting the amyloidogenic pathway and reducing α-synuclein cellulartoxicity. Hum. Mol. Genet., 2014; 23: 5615 –5629
  Google Scholar
• 86. Polymenidou M., Lagier-Tourenne C., Hutt K.R., Huelga S.C., MoranJ., Liang T.Y., Ling S.C., Sun E., Wancewicz E., Mazur C., KordasiewiczH., Sedaghat Y., Donohue J.P., Shiue L., Bennett C.F. i wsp.: Longpre-mRNA depletion and RNA missplicing contribute to neuronalvulnerability from loss of TDP-43. Nat. Neurosci., 2011; 14: 459 –468
  Google Scholar
• 87. Prasad A., Sivalingam V., Bharathi V., Girdhar A., Patel B.K.: Theamyloidogenicity of a C-terminal region of TDP-43 implicated inamyotrophic lateral sclerosis can be affected by anions, acetylationand homodimerization. Biochimie, 2018; 150: 76 –87
  Google Scholar
• 88. Qureshi H.Y., Paudel H.K.: Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-synuclein mutationspromote Tau protein phosphorylation at Ser262 and destabilizemicrotubule cytoskeleton in vitro. J. Biol. Chem., 2011; 286: 5055 –5068
  Google Scholar
• 89. Ramaswami M., Taylor J.P., Parker R.: Altered ribostasis: RNAproteingranules in degenerative disorders. Cell, 2013; 154: 727 –736
  Google Scholar
• 90. Rocca W.A.: The burden of Parkinson’s disease: A worldwide perspective.Lancet Neurol., 2018; 17: 928 –929
  Google Scholar
• 91. Russo M.A., Tomino C., Vernucci E., Limana F., Sansone L., FrustaciA., Tafani M.: Hypoxia and inflammation as a consequence of β-fibrilaccumulation: A perspective view for new potential therapeutic targets.Oxid. Med. Cell. Longev., 2019; 2019: 7935310
  Google Scholar
• 92. Salvatori I., Ferri A., Scaricamazza S., Giovannelli I., Serrano A.,Rossi S., D’Ambrosi N., Cozzolino M., Giulio A.D., Moreno S., Valle C.,Carrì M.T.: Differential toxicity of TAR DNA-binding protein 43 isoformsdepends on their submitochondrial localization in neuronalcells. J. Neurochem., 2018; 146: 585 –597
  Google Scholar
• 93. Saman S., Kim W., Raya M., Visnick Y., Miro S., Saman S., JacksonB., McKee A.C., Alvarez V.E., Lee N.C., Hall G.F.: Exosome-associatedtau is secreted in tauopathy models and is selectively phosphorylatedin cerebrospinal fluid in early Alzheimer disease. J. Biol. Chem.,2012; 287: 3842 –3849
  Google Scholar
• 94. Siddiqui I.J., Pervaiz N., Abbasi A.A.: The Parkinson Disease geneSNCA: Evolutionary and structural insights with pathological implication.Sci. Rep., 2016; 6: 24475
  Google Scholar
• 95. Singleton A.B., Farrer M., Johnson J., Singleton A., Hague S., KachergusJ., Hulihan M., Peuralinna T., Dutra A., Nussbaum R., Lincoln S.,Crawley A., Hanson M., Maraganore D., Adler C. i wsp.: α-synucleinlocus triplication causes Parkinson’s disease. Science, 2003; 302: 841
  Google Scholar
• 96. Spillantini M.G., Divane A., Goedert M.: Assignment of humanα-synuclein (SNCA) and β-synuclein (SNCB) genes to chromosomes4q21 and 5q35. Genomics, 1995; 27: 379 –381
  Google Scholar
• 97. Sprovieri T., Ungaro C., Perrone B., Naimo G.D., Spataro R., CavallaroS., La Bella V., Conforti F.L.: A novel S379A TARDBP mutation associatedto late-onset sporadic ALS. Neurol. Sci., 2019; 40: 2111 –2118
  Google Scholar
• 98. Stefanoska K., Volkerling A., Bertz J., Poljak A., Ke Y.D., Ittner L.M.,Ittner A.: An N-terminal motif unique to primate tau enables differentialprotein-protein interactions. J. Biol. Chem., 2018; 293: 3710 –3719
  Google Scholar
• 99. Strang K.H., Golde T.E., Giasson B.I.: MAPT mutations, tauopathy,and mechanisms of neurodegeneration. Lab. Invest., 2019; 99: 912 –928
  Google Scholar
• 100. Sultan A., Nesslany F., Violet M., Bégard S., Loyens A., TalahariS., Mansuroglu Z., Marzin D., Sergeant N., Humez S., Colin M., BonnefoyE., Buée L., Galas M.C.: Nuclear tau, a key player in neuronal DNAprotection. J. Biol. Chem., 2011; 286: 4566 –4575
  Google Scholar
• 101. Takeda T.: Possible concurrence of TDP-43, tau and other proteinsin amyotrophic lateral sclerosis/frontotemporal lobar degeneration.Neuropathology, 2018; 38: 72 –81
  Google Scholar
• 102. TARDBP TAR DNA binding protein [Homo sapiens (human)] –Gene – NCBI. https://www.ncbi.nlm.nih.gov/gene/23435 (02.06.2020)
  Google Scholar
• 103. Turner B.J., Bäumer D., Parkinson N.J., Scaber J., Ansorge O.,Talbot K.: TDP-43 expression in mouse models of amyotrophic lateralsclerosis and spinal muscular atrophy. BMC Neurosci., 2008; 9: 104
  Google Scholar
• 104. van Swieten J., Spillantini M.G.: Hereditary frontotemporal dementiacaused by Tau gene mutations. Brain Pathol., 2007; 17: 63 –73
  Google Scholar
• 105. Vicente Miranda H., Cássio R., Correia-Guedes L., Gomes M.A.,Chegão A., Miranda E., Soares T., Coelho M., Rosa M.M., Ferreira J.J.,Outeiro T.F.: Posttranslational modifications of blood-derived alphasynucleinas biochemical markers for Parkinson’s disease. Sci. Rep.,2017; 7: 13713
  Google Scholar
• 106. von Bergen M., Barghorn S., Biernat J., Mandelkow E.M., MandelkowE.: Tau aggregation is driven by a transition from random coilto beta sheet structure. Biochim. Biophys. Acta, 2005; 1739: 158 –166
  Google Scholar
• 107. Wang Y.T., Kuo P.H., Chiang C.H., Liang J.R., Chen Y.R., Wang S.,Shen J.C., Yuan H.S.: The truncated C-terminal RNA recognition motifof TDP-43 protein plays a key role in forming proteinaceous aggregates.J. Biol. Chem., 2013; 288: 9049 –9057
  Google Scholar
• 108. Watanabe A., Hasegawa M., Suzuki M., Takio K., Morishima-Kawashima M., Titani K., Arai T., Kosik K.S., Ihara Y.: In vivo phosphorylationsites in fetal and adult rat tau. J. Biol. Chem., 1993; 268: 25712 –25717
  Google Scholar
• 109. Wilhelmsen K.C., Lynch T., Pavlou E., Higgins M., Nygaard T.G.:Localization of disinhibition-dementia-parkinsonism-amyotrophycomplex to 17q21-22. Am. J. Hum. Genet., 1994; 55: 1159 –1165
  Google Scholar
• 110. Wong Y.C., Krainc D.: α-synuclein toxicity in neurodegeneration:mechanism and therapeutic strategies. Nat. Med., 2017; 23: 1 –13
  Google Scholar
• 111. Yamada K., Holth J.K., Liao F., Stewart F.R., Mahan T.E., Jiang H.,Cirrito J.R., Patel T.K., Hochgräfe K., Mandelkow E.M., Holtzman D.M.:Neuronal activity regulates extracellular tau in vivo. J. Exp. Med.,2014; 211: 387 –393
  Google Scholar
• 112. Yang W., Wang X., Duan C., Lu L., Yang H.: Alpha-synuclein overexpressionincreases phosphoprotein phosphatase 2A levels via formationof calmodulin/Src complex. Neurochem. Int., 2013; 63: 180–194
  Google Scholar
• 113. Yarchoan M., Toledo J.B., Lee E.B., Arvanitakis Z., Kazi H., HanL.Y., Louneva N., Lee V.M., Kim S.F., Trojanowski J.Q., Arnold S.E.: Abnormalserine phosphorylation of insulin receptor substrate 1 is associatedwith tau pathology in Alzheimer’s disease and tauopathies.Acta Neuropathol., 2014; 128: 679 –689
  Google Scholar
• 114. Yuan A., Kumar A., Peterhoff C., Duff K., Nixon R.A.: Axonal transportrates in vivo are unaffected by tau deletion or overexpression inmice. J. Neurosci., 2008; 28: 1682 –1687
  Google Scholar
• 115. Yuzwa S.A., Macauley M.S., Heinonen J.E., Shan X., Dennis R.J.,He Y., Whitworth G.E., Stubbs K.A., McEachern E.J., Davies G.J., VocadloD.J.: A potent mechanism-inspired O-GlcNAcase inhibitor that blocksphosphorylation of tau in vivo. Nat. Chem. Biol., 2008; 4: 483 –490
  Google Scholar
• 116. Zarranz J.J., Alegre J., Gómez-Esteban J.C., Lezcano E., Ros R.,Ampuero I., Vidal L., Hoenicka J., Rodriguez O., Atarés B., Llorens V.,Gomez Tortosa E., del Ser T., Muñoz D.G., de Yebenes J.G.: The newmutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia.Ann. Neurol., 2004; 55: 164 –173
  Google Scholar
• 117. Zempel H., Thies E., Mandelkow E., Mandelkow E.M.: Aβ oligomerscause localized Ca2+ elevation, missorting of endogenous Tau intodendrites, Tau phosphorylation, and destruction of microtubules andspines. J. Neurosci., 2010; 30: 11938 –11950
  Google Scholar
• 118. Zhang Y., Chen K., Sloan S.A., Bennett M.L., Scholze A.R., O’KeeffeS., Phatnani H.P., Guarnieri P., Caneda C., Ruderisch N., Deng S., Liddelow S.A., Zhang C., Daneman R., Maniatis T. i wsp.: An RNA-sequencingtranscriptome and splicing database of glia, neurons, andvascular cells of the cerebral cortex. J. Neurosci., 2014; 34: 11929 –11947
  Google Scholar
• 119. Zhang Y.W., Thompson R., Zhang H., Xu H.: APP processing inAlzheimer’s disease. Mol. Brain., 2011; 4: 3
  Google Scholar
• 120. Zheng W.H., Bastianetto S., Mennicken F., Ma W., Kar S.: Amyloidbeta peptide induces tau phosphorylation and loss of cholinergic neuronsin rat primary septal cultures. Neuroscience, 2002; 115: 201 –211
  Google Scholar

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