Skip to main content
SpringerLink
Log in

Neuroprotektive Therapien bei Tauopathien

Neuroprotective treatment of tauopathies

  • Leitthema
  • Published:
Der Nervenarzt Aims and scope Submit manuscript

Zusammenfassung

Tau-Pathologie gilt heute als Hauptverursacher eines breiten Spektrums neurodegenerativer Erkrankungen, die als Tauopathien zusammengefasst werden. Dazu gehören primäre Tauopathien, bei denen Tau die Hauptrolle bei der Pathogenese spielt, sowie sekundäre Tauopathien wie die Alzheimer-Krankheit, bei der neben Tau auch Amyloid‑β eine wesentliche Rolle im Krankheitsprozess zukommt. Zu den primären Tauopathien gehören unter anderem die progressive supranukleäre Blickparese, die kortikobasale Degeneration, die Pick-Krankheit und seltene hereditäre Tauopathien, welche als frontotemporale Lobärdegeneration mit MAPT(„microtubule-associated protein tau“)-Mutation bezeichnet werden. Tauopathien unterscheiden sich pathologisch durch die betroffenen Hirnregionen und Zelltypen sowie durch die biochemischen Merkmale des aggregierten Tau-Proteins. Verschiedene Tau-zentrierte neuroprotektive Therapieansätze befinden sich aktuell in der präklinischen und klinischen Entwicklung. Dabei werden unterschiedliche Mechanismen, wie die Verringerung der Tau-Expression, die Hemmung der Tau-Aggregation, das Auflösen von Tau-Aggregaten, die Verstärkung der zellulären Mechanismen zur Beseitigung toxischer Formen von Tau, die Stabilisierung von Mikrotubuli und die Hemmung der interzellulären Ausbreitung von Tau, untersucht. In dieser Übersichtsarbeit geben wir einen Überblick über Tauopathien und die aktuellen Konzepte zur Entwicklung krankheitsmodifizierender Therapien.

Abstract

Tau pathology is now considered to be the main cause of a wide spectrum of neurodegenerative diseases, which are collectively referred to as tauopathies. These include primary tauopathies, in which tau plays the main role in the pathogenesis as well as secondary tauopathies, such as Alzheimer’s disease, in which amyloid beta also plays a substantial role in the disease process in addition to the tau pathology. Primary tauopathies include progressive supranuclear palsy, corticobasal degeneration, Pick’s disease and rare hereditary tauopathies, which are referred to as frontotemporal lobar degeneration with microtubule-associated protein tau (MAPT) mutation. Tauopathies differ from each other pathologically by the affected brain regions and cell types as well as by the biochemical characteristics of the aggregated tau protein. Various tau-centered neuroprotective treatment approaches are currently in preclinical and clinical development. They target different mechanisms, including the reduction of tau expression, inhibition of tau aggregation, dissolution of tau aggregates, improvement of cellular mechanisms to eliminate toxic tau species, stabilization of microtubules and prevention of intercellular tau spreading. This review article gives an overview of tauopathies and the current concepts for the development of disease-modifying treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Apetauerova D, Scala SA, Hamill RW, Simon DK, Pathak S, Ruthazer R, Standaert DG, Yacoubian TA (2016) CoQ10 in progressive supranuclear palsy. Neurol Neuroimmunol Neuroinflamm 3:e266. https://doi.org/10.1212/NXI.0000000000000266

    Article  PubMed  PubMed Central  Google Scholar 

  2. Arbo BD, André-Miral C, Nasre-Nasser RG, Schimith LE, Santos MG, Costa-Silva D, Muccillo-Baisch AL, Hort MA (2020) Resveratrol derivatives as potential treatments for alzheimer’s and parkinson’s disease. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2020.00103

    Article  PubMed  PubMed Central  Google Scholar 

  3. Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol J‑C, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Höglinger GU, Koestler M, Jack CR, Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH (2014) Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol 13:676–685. https://doi.org/10.1016/S1474-4422(14)70088-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Braak H, Braak E (1995) Staging of Alzheimers disease-related neurofibrillary changes. Neurobiol Aging 16(3):271–8

    Article  CAS  Google Scholar 

  5. Brendel M, Barthel H, van Eimeren T, Marek K, Beyer L, Song M, Palleis C, Gehmeyr M, Fietzek U, Respondek G, Sauerbeck J, Nitschmann A, Zach C, Hammes J, Barbe MT, Onur O, Jessen F, Saur D, Schroeter ML, Rumpf J‑J, Rullmann M, Schildan A, Patt M, Neumaier B, Barret O, Madonia J, Russell DS, Stephens A, Roeber S, Herms J, Bötzel K, Classen J, Bartenstein P, Villemagne V, Levin J, Höglinger GU, Drzezga A, Seibyl J, Sabri O (2020) Assessment of 18 F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurol 77:1408. https://doi.org/10.1001/jamaneurol.2020.2526

    Article  PubMed  Google Scholar 

  6. Crowe A, James MJ, Lee VM‑Y, Smith AB, Trojanowski JQ, Ballatore C, Brunden KR (2013) Aminothienopyridazines and methylene blue affect tau fibrillization via cysteine oxidation. J Biol Chem 288:11024–11037. https://doi.org/10.1074/jbc.M112.436006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. DeVos SL, Miller RL, Schoch KM, Holmes BB, Kebodeaux CS, Wegener AJ, Chen G, Shen T, Tran H, Nichols B, Zanardi TA, Kordasiewicz HB, Swayze EE, Bennett CF, Diamond MI, Miller TM (2017) Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci Transl Med 9:eaag481. https://doi.org/10.1126/scitranslmed.aag0481

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Garwood CJ, Cooper JD, Hanger DP, Noble W (2010) Anti-inflammatory impact of minocycline in a mouse model of tauopathy. Front Psychiatry. https://doi.org/10.3389/fpsyt.2010.00136

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, Hardlund JH, Moebius HJ, Bentham P, Kook KA, Wischik DJ, Schelter BO, Davis CS, Staff RT, Bracoud L, Shamsi K, Storey JMD, Harrington CR, Wischik CM (2016) Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 388:2873–2884. https://doi.org/10.1016/S0140-6736(16)31275-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Golbe LI, Ohman-Strickland PA (2007) A clinical rating scale for progressive supranuclear palsy. Brain 130:1552–1565. https://doi.org/10.1093/brain/awm032

    Article  PubMed  Google Scholar 

  11. Hastings NB, Wang X, Song L, Butts BD, Grotz D, Hargreaves R, Hess FJ, Hong K‑LK, Huang CR‑R, Hyde L, Laverty M, Lee J, Levitan D, Lu SX, Maguire M, Mahadomrongkul V, McEachern EJ, Ouyang X, Rosahl TW, Selnick H, Stanton M, Terracina G, Vocadlo DJ, Wang G, Duffy JL, Parker EM, Zhang L (2017) Inhibition of O‑GlcNAcase leads to elevation of O‑GlcNAc tau and reduction of tauopathy and cerebrospinal fluid tau in rTg4510 mice. Mol Neurodegener 12:39. https://doi.org/10.1186/s13024-017-0181-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Höglinger GU, Huppertz H‑J, Wagenpfeil S, Andrés MV, Belloch V, León T, Del Ser T, TAUROS MRI Investigators (2014) Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial. Mov Disord 29:479–487. https://doi.org/10.1002/mds.25815

    Article  PubMed  CAS  Google Scholar 

  13. Kovacs GG, Respondek G, van Eimeren T, Höller E, Levin J, Müller U, Schwarz S, Rösler TW, Schweyer K, Höglinger GU (2018) Tauopathien. Nervenarzt 89:1083–1094. https://doi.org/10.1007/s00115-018-0584-3

    Article  PubMed  CAS  Google Scholar 

  14. Krüger U, Wang Y, Kumar S, Mandelkow E‑M (2012) Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiol Aging 33:2291–2305. https://doi.org/10.1016/j.neurobiolaging.2011.11.009

    Article  PubMed  CAS  Google Scholar 

  15. Lang AE, Stebbins GT, Wang P, Jabbari E, Lamb R, Morris H, Boxer AL, Boxer A, Boeve B, Dickerson B, Grossman M, Litvan I, Ljubenkov P, Pantelyat A, Rojas-Martinez J, Tartaglia M‑C, Wills A‑M, Morris H, Amar K, Capps E, Carey G, Church A, Critchley P, Ghosh B, Houlden H, Hu M, Jabbari E, Kobylecki C, Massey L, Molloy S, Nath U, Pavese N, Rowe JB (2020) The cortical basal ganglia functional scale (CBFS): development and preliminary validation. Parkinsonism Relat Disord 79:121–126. https://doi.org/10.1016/j.parkreldis.2020.08.021

    Article  PubMed  Google Scholar 

  16. Leclair-Visonneau L, Rouaud T, Debilly B, Durif F, Houeto J‑L, Kreisler A, Defebvre L, Lamy E, Volteau C, Nguyen J‑M, Le Dily S, Damier P, Boutoleau-Bretonnière C, Lejeune P, Derkinderen P (2016) Randomized placebo-controlled trial of sodium valproate in progressive supranuclear palsy. Clin Neurol Neurosurg 146:35–39. https://doi.org/10.1016/j.clineuro.2016.04.021

    Article  PubMed  Google Scholar 

  17. Litvinchuk A, Wan Y‑W, Swartzlander DB, Chen F, Cole A, Propson NE, Wang Q, Zhang B, Liu Z, Zheng H (2018) Complement C3aR inactivation attenuates tau pathology and reverses an immune network deregulated in tauopathy models and Alzheimer’s disease. Neuron 100:1337–1353.e5. https://doi.org/10.1016/j.neuron.2018.10.031

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Grötsch M‑T, Respondek G, Colosimo C, Compta Y, Corvol JC, Ferreira J, Huber MK, Klietz M, Krey LFM, Levin J, Jecmenica-Lukic M, Macías-García D, Meissner WG, Mir P, Movement Disorder Society-Endorsed PSP Study Group (2021) A modified progressive supranuclear palsy rating scale. Mov Disord 36(5):1203–1215. https://doi.org/10.1002/mds.28470

    Article  PubMed  Google Scholar 

  19. Melis V, Magbagbeolu M, Rickard JE, Horsley D, Davidson K, Harrington KA, Goatman K, Goatman EA, Deiana S, Close SP, Zabke C, Stamer K, Dietze S, Schwab K, Storey JMD, Harrington CR, Wischik CM, Theuring F, Riedel G (2015) Effects of oxidized and reduced forms of methylthioninium in two transgenic mouse tauopathy models. Behav Pharmacol 26:353–368. https://doi.org/10.1097/FBP.0000000000000133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Min S‑W, Sohn PD, Li Y, Devidze N, Johnson JR, Krogan NJ, Masliah E, Mok S‑A, Gestwicki JE, Gan L (2018) SIRT1 deacetylates tau and reduces pathogenic tau spread in a mouse model of tauopathy. J Neurosci 38:3680–3688. https://doi.org/10.1523/JNEUROSCI.2369-17.2018

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Nijholt DA, van Haastert ES, Rozemuller AJ, Scheper W, Hoozemans JJ (2012) The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathies. J Pathol 226:693–702. https://doi.org/10.1002/path.3969

    Article  PubMed  CAS  Google Scholar 

  22. Novak P, Schmidt R, Kontsekova E, Zilka N, Kovacech B, Skrabana R, Vince-Kazmerova Z, Katina S, Fialova L, Prcina M, Parrak V, Dal-Bianco P, Brunner M, Staffen W, Rainer M, Ondrus M, Ropele S, Smisek M, Sivak R, Winblad B, Novak M (2017) Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol 16:123–134. https://doi.org/10.1016/S1474-4422(16)30331-3

    Article  PubMed  CAS  Google Scholar 

  23. Piot I, Schweyer K, Respondek G, Stamelou M, Sckopke P, Schenk T, Goetz CG, Stebbins GT, Höglinger GU, Gasser T, Hermann A, Höglinger G, Höllerhage M, Kimmich O, Klockgether T, Levin J, Machetanz G, Osterrath A, Palleis C, Prudlo J, Spottke A, Berg D, Bürk K, Claßen J, Eggers C, Greuel A, Grimm M, Hermann L, Iankova V, Jahn K, Jost W, Klietz M, Kühn A, Marxreiter F, Paschen S, Poetter-Nerger M, Preisl M, Prilop L, Tönges L, Trenkwalder C, Warnecke T, Wegner F, Winkler J, Antonini A, Colosimo C, Compta Y, Corvol J, Li I, Höglinger GU, Litvan I, Nilsson C, Pantelyat A, Respondek G, Stamelou M (2020) The progressive Supranuclear palsy clinical deficits scale. Mov Disord 35:650–661. https://doi.org/10.1002/mds.27964

    Article  PubMed  Google Scholar 

  24. Rojas JC, Karydas A, Bang J, Tsai RM, Blennow K, Liman V, Kramer JH, Rosen H, Miller BL, Zetterberg H, Boxer AL (2016) Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol 3:216–225. https://doi.org/10.1002/acn3.290

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Ryan JM, Quattropani A, Abd-Elaziz K, den Daas I, Schneider M, Ousson S, Neny M, Sand A, Hantson J, Permanne B, Wiessner C, Beher D (2018) O1-12-05: phase 1 study in healthy volunteers of the O‑GlcNAcase inhibitor ASN120290 as a novel therapy for progressive supranuclear palsy and related tauopathies. Alzheimers Dement 14:P251–P251. https://doi.org/10.1016/j.jalz.2018.06.2400

    Article  Google Scholar 

  26. Saijo E, Metrick MA, Koga S, Parchi P, Litvan I, Spina S, Boxer A, Rojas JC, Galasko D, Kraus A, Rossi M, Newell K, Zanusso G, Grinberg LT, Seeley WW, Ghetti B, Dickson DW, Caughey B (2020) 4‑Repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration. Acta Neuropathol 139:63–77. https://doi.org/10.1007/s00401-019-02080-2

    Article  PubMed  CAS  Google Scholar 

  27. Schaeffer V, Lavenir I, Ozcelik S, Tolnay M, Winkler DT, Goedert M (2012) Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy. Brain 135:2169–2177. https://doi.org/10.1093/brain/aws143

    Article  PubMed  PubMed Central  Google Scholar 

  28. Schaler AW, Myeku N (2018) Cilostazol, a phosphodiesterase 3 inhibitor, activates proteasome-mediated proteolysis and attenuates tauopathy and cognitive decline. Transl Res 193:31–41. https://doi.org/10.1016/j.trsl.2017.11.004

    Article  PubMed  CAS  Google Scholar 

  29. Selnick HG, Hess JF, Tang C, Liu K, Schachter JB, Ballard JE, Marcus J, Klein DJ, Wang X, Pearson M, Savage MJ, Kaul R, Li T‑S, Vocadlo DJ, Zhou Y, Zhu Y, Mu C, Wang Y, Wei Z, Bai C, Duffy JL, McEachern EJ (2019) Discovery of MK-8719, a potent O‑GlcNAcase inhibitor as a potential treatment for tauopathies. J Med Chem 62:10062–10097. https://doi.org/10.1021/acs.jmedchem.9b01090

    Article  PubMed  CAS  Google Scholar 

  30. Seripa D, Solfrizzi V, Imbimbo BP, Daniele A, Santamato A, Lozupone M, Zuliani G, Greco A, Logroscino G, Panza F (2016) Tau-directed approaches for the treatment of Alzheimer’s disease: focus on leuco-methylthioninium. Expert Rev Neurother 16:259–277. https://doi.org/10.1586/14737175.2016.1140039

    Article  PubMed  CAS  Google Scholar 

  31. Shimada K, Motoi Y, Ishiguro K, Kambe T, Matsumoto S‑E, Itaya M, Kunichika M, Mori H, Shinohara A, Chiba M, Mizuno Y, Ueno T, Hattori N (2012) Long-term oral lithium treatment attenuates motor disturbance in tauopathy model mice: implications of autophagy promotion. Neurobiol Dis 46:101–108. https://doi.org/10.1016/j.nbd.2011.12.050

    Article  PubMed  CAS  Google Scholar 

  32. Smith HL, Mallucci GR (2016) The unfolded protein response: mechanisms and therapy of neurodegeneration. Brain 139:2113–2121. https://doi.org/10.1093/brain/aww101

    Article  PubMed  PubMed Central  Google Scholar 

  33. Stamelou M, Reuss A, Pilatus U, Magerkurth J, Niklowitz P, Eggert KM, Krisp A, Menke T, Schade-Brittinger C, Oertel WH, Höglinger GU (2008) Short-term effects of coenzyme Q 10 in progressive supranuclear palsy: a randomized, placebo-controlled trial. Mov Disord 23:942–949. https://doi.org/10.1002/mds.22023

    Article  PubMed  Google Scholar 

  34. Sud R, Geller ET, Schellenberg GD (2014) Antisense-mediated exon skipping decreases tau protein expression: a potential therapy for tauopathies. Mol Ther Nucleic Acids 3:e180. https://doi.org/10.1038/mtna.2014.30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Theunis C, Crespo-Biel N, Gafner V, Pihlgren M, López-Deber MP, Reis P, Hickman DT, Adolfsson O, Chuard N, Ndao DM, Borghgraef P, Devijver H, Van Leuven F, Pfeifer A, Muhs A (2013) Efficacy and safety of a liposome-based vaccine against protein tau, assessed in Tau.P301L mice that model tauopathy. PLoS One 8:e72301. https://doi.org/10.1371/journal.pone.0072301

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tolosa E, Litvan I, Höglinger GU, Burn D, Lees A, Andrés MV, Gómez-Carrillo B, León T, Del Ser T, Gómez JC, Tijero B, Berganzo K, García de Yebenes J, Lopez Sendón JL, Garcia G, Tolosa E, Buongiorno MT, Bargalló N, Burguera JA, Martinez I, Ruiz-Martínez J, Narrativel I, Vivancos F, Ybot I, Aguilar M, Quilez P, Boada M, Lafuente A, Hernandez I, López-Lozano JJ, Mata M, Kupsch A, Lipp A, Ebersbach G, Schmidt T, Hahn K, Höglinger G, Höllerhage M, Oertel WH, Respondek G, Stamelou M, Reichmann H, Wolz M, Schneider C, Klingelhöfer L, Berg D, Maetzler W, Srulijes KK, Ludolph A, Kassubek J, Steiger M, Tyler K, Morris L, Lees A, Ling H, Hauser R, McClain T, Truong D, Jenkins S, Litvan I, Houghton D, Ferrara J, Bordelon Y, Gratiano A, Golbe L, Mark M, Uitti R, Ven Gerpen J (2014) A phase 2 trial of the GSK‑3 inhibitor tideglusib in progressive supranuclear palsy. Mov Disord. https://doi.org/10.1002/mds.25824

    Article  PubMed  PubMed Central  Google Scholar 

  37. VandeVrede L, Dale ML, Fields S, Frank M, Hare E, Heuer HW, Keith K, Koestler M, Ljubenkov PA, McDermott D, Ohanesian N, Richards J, Rojas JC, Thijssen EH, Walsh C, Wang P, Wolf A, Quinn JF, Tsai R, Boxer AL (2020) Open-label phase 1 futility studies of salsalate and young plasma in progressive supranuclear palsy. Mov Disord Clin Pract 7:440–447. https://doi.org/10.1002/mdc3.12940

    Article  PubMed  PubMed Central  Google Scholar 

  38. Waldherr SM, Strovas TJ, Vadset TA, Liachko NF, Kraemer BC (2019) Constitutive XBP-1s-mediated activation of the endoplasmic reticulum unfolded protein response protects against pathological tau. Nat Commun 10:4443. https://doi.org/10.1038/s41467-019-12070-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Whitwell JL, Tosakulwong N, Botha H, Ali F, Clark HM, Duffy JR, Utianski RL, Stevens CA, Weigand SD, Schwarz CG, Senjem ML, Jack CR, Lowe VJ, Ahlskog JE, Dickson DW, Josephs KA (2020) Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants. Neuroimage Clin 25:102152. https://doi.org/10.1016/j.nicl.2019.102152

    Article  PubMed  Google Scholar 

  40. Whitwell JL, Tosakulwong N, Schwarz CG, Botha H, Senjem ML, Spychalla AJ, Ahlskog JE, Knopman DS, Petersen RC, Jack CR, Lowe VJ, Josephs KA (2019) MRI outperforms [18F]AV-1451 PET as a longitudinal biomarker in progressive supranuclear palsy. Mov Disord 34:105–113. https://doi.org/10.1002/mds.27546

    Article  PubMed  CAS  Google Scholar 

  41. Yadikar H, Torres I, Aiello G, Kurup M, Yang Z, Lin F, Kobeissy F, Yost R, Wang KK (2020) Screening of tau protein kinase inhibitors in a tauopathy-relevant cell-based model of tau hyperphosphorylation and oligomerization. PLoS ONE 15:e224952. https://doi.org/10.1371/journal.pone.0224952

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Yuzwa SA, Macauley MS, Heinonen JE, Shan X, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ, Vocadlo DJ (2008) A potent mechanism-inspired O‑GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol 4:483–490. https://doi.org/10.1038/nchembio.96

    Article  PubMed  CAS  Google Scholar 

  43. Wischik CM, Edwards PC, Lai RY, Roth M, Harrington CR (1996) Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A 93:11213–11218. https://doi.org/10.1073/pnas.93.20.11213

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Yuan SH, Hiramatsu N, Liu Q, Sun XV, Lenh D, Chan P, Chiang K, Koo EH, Kao AS, Litvan I, Lin JH (2018) Tauopathy-associated PERK alleles are functional hypomorphs that increase neuronal vulnerability to ER stress. Hum Mol Genet. https://doi.org/10.1093/hmg/ddy297

    Article  PubMed  PubMed Central  Google Scholar 

  45. Höglinger GU, Litvan I, Mendonca N et al (2021) Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial. Lancet Neurol 20:182–192. https://doi.org/10.1016/S1474-4422(20)30489-0

    Article  PubMed  Google Scholar 

  46. Yu J‑T, Lang AE, Boxer AL, Yu J‑T, Golbe LI, Litvan I, Lang AE, Höglinger GU (2017) Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Lancet Neurol. https://doi.org/10.1016/S1474-4422(17)30157-6

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zetterberg H (2016) Neurofilament light: a dynamic cross-disease fluid biomarker for neurodegeneration. Neuron 91:1–3. https://doi.org/10.1016/j.neuron.2016.06.030

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Neurologie, Medizinische Hochschule Hannover (MHH), Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    Gesine Respondek, Lea Krey, Meret Huber, Henning Pflugrad, Florian Wegner &  Günter U. Höglinger

  2. Standort München, Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), München, Deutschland

    Gesine Respondek &  Günter U. Höglinger

  3. Zentrum für Systemische Neurowissenschaften, Hannover, Deutschland

    Florian Wegner &  Günter U. Höglinger

Authors
  1. Gesine Respondek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lea Krey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meret Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henning Pflugrad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Florian Wegner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Günter U. Höglinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Günter U. Höglinger.

Ethics declarations

Interessenkonflikt

G. Respondek hat eine bezahlte Beratertätigkeit bei UCB Pharma ausgeübt. H. Pflugrad hat Honorar für ein Interview von Merz Pharmaceuticals GmbH erhalten. G.U. Höglinger übt eine bezahlte Beratertätigkeit für Abbvie, Alzprotect, Asceneuron, Bial, Biogen, Biohaven, Kyowa Kirin, Lundbeck, Novartis, Retrotope, Roche, Sanofi, UCB aus und erhielt Honorar für einen wissenschaftlichen Vortrag von Abbvie, Bayer Vital, Bial, Biogen, Bristol Myers Squibb, Kyowa Kirin, Roche, Teva, UCB, Zambon. L. Krey, M. Huber und F. Wegner geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Respondek, G., Krey, L., Huber, M. et al. Neuroprotektive Therapien bei Tauopathien. Nervenarzt 92, 1227–1238 (2021). https://doi.org/10.1007/s00115-021-01210-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00115-021-01210-0

Schlüsselwörter

Keywords

Search

Navigation