Login Register Cart 0
Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Microtubule-modulating Agents in the Fight Against Neurodegeneration: Will it ever Work?

Author(s): Ahmed Soliman , Lidia Bakota and Roland Brandt *

Volume 20, Issue 4, 2022

Published on: 24 February, 2022

Page: [782 - 798] Pages: 17

DOI: 10.2174/1570159X19666211201101020

open access plus

Abstract

The microtubule skeleton plays an essential role in nerve cells as the most important structural determinant of morphology and as a highway for axonal transport processes. Many neurodegenerative diseases are characterized by changes in the structure and organization of microtubules and microtubule-regulating proteins such as the microtubule-associated protein tau, which exhibits characteristic changes in a whole class of diseases collectively referred to as tauopathies. Changes in the dynamics of microtubules appear to occur early under neurodegenerative conditions and are also likely to contribute to age-related dysfunction of neurons. Thus, modulating microtubule dynamics and correcting impaired microtubule stability can be a useful neuroprotective strategy to counteract the disruption of the microtubule system in disease and aging. In this article, we review current microtubule- directed approaches for the treatment of neurodegenerative diseases with microtubules as a drug target, tau as a drug target, and post-translational modifications as potential modifiers of the microtubule system. We discuss limitations of the approaches that can be traced back to the rather unspecific mechanism of action, which causes undesirable side effects in non-neuronal cell types or which are due to the disruption of non-microtubule-related interactions. We also develop some thoughts on how the specificity of the approaches can be improved and what further targets could be used for modulating substances.

Keywords: Microtubules, cytoskeleton, neurodegenerative diseases, tauopathies, microtubule-modulating drugs, neuron.

« Previous Next »
Graphical Abstract

[1]
Cleveland, D.W.; Hoffman, P.N. Neuronal and glial cytoskeletons. Curr. Opin. Neurobiol., 1991, 1(3), 346-353.
[http://dx.doi.org/10.1016/0959-4388(91)90051-8] [PMID: 1821676]
[2]
Lasek, R.J.; Garner, J.A.; Brady, S.T. Axonal transport of the cytoplasmic matrix. J. Cell Biol., 1984, 99(1 Pt 2), 212s-221s.
[http://dx.doi.org/10.1083/jcb.99.1.212s] [PMID: 6378920]
[3]
Penazzi, L.; Bakota, L.; Brandt, R. Microtubule dynamics in neuronal development, plasticity, and neurodegeneration. Int. Rev. Cell Mol. Biol., 2016, 321, 89-169.
[http://dx.doi.org/10.1016/bs.ircmb.2015.09.004] [PMID: 26811287]
[4]
Black, M.M.; Baas, P.W. The basis of polarity in neurons. Trends Neurosci., 1989, 12(6), 211-214.
[http://dx.doi.org/10.1016/0166-2236(89)90124-0] [PMID: 2473556]
[5]
Mitchison, T.; Kirschner, M. Cytoskeletal dynamics and nerve growth. Neuron, 1988, 1(9), 761-772.
[http://dx.doi.org/10.1016/0896-6273(88)90124-9] [PMID: 3078414]
[6]
Hahn, I.; Voelzmann, A.; Liew, Y.T.; Costa-Gomes, B.; Prokop, A. The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology. Neural Dev., 2019, 14(1), 11.
[http://dx.doi.org/10.1186/s13064-019-0134-0] [PMID: 31706327]
[7]
Baas, P.W.; Rao, A.N.; Matamoros, A.J.; Leo, L. Stability properties of neuronal microtubules. Cytoskeleton (Hoboken), 2016, 73(9), 442-460.
[http://dx.doi.org/10.1002/cm.21286] [PMID: 26887570]
[8]
Avila, J.; Domínguez, J.; Díaz-Nido, J. Regulation of microtubule dynamics by microtubule-associated protein expression and phosphorylation during neuronal development. Int. J. Dev. Biol., 1994, 38(1), 13-25.
[PMID: 8074993]
[9]
Grenningloh, G.; Soehrman, S.; Bondallaz, P.; Ruchti, E.; Cadas, H. Role of the microtubule destabilizing proteins SCG10 and stathmin in neuronal growth. J. Neurobiol., 2004, 58(1), 60-69.
[http://dx.doi.org/10.1002/neu.10279] [PMID: 14598370]
[10]
Yu, W.; Qiang, L.; Solowska, J.M.; Karabay, A.; Korulu, S.; Baas, P.W. The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches. Mol. Biol. Cell, 2008, 19(4), 1485-1498.
[http://dx.doi.org/10.1091/mbc.e07-09-0878] [PMID: 18234839]
[11]
van de Willige, D.; Hoogenraad, C.C.; Akhmanova, A. Microtubule plus-end tracking proteins in neuronal development. Cell. Mol. Life Sci., 2016, 73(10), 2053-2077.
[http://dx.doi.org/10.1007/s00018-016-2168-3] [PMID: 26969328]
[12]
Trushina, N.I.; Mulkidjanian, A.Y.; Brandt, R. The microtubule skeleton and the evolution of neuronal complexity in vertebrates. Biol. Chem., 2019, 400(9), 1163-1179.
[http://dx.doi.org/10.1515/hsz-2019-0149] [PMID: 31116700]
[13]
Kosik, K.S.; Finch, E.A. MAP2 and tau segregate into dendritic and axonal domains after the elaboration of morphologically distinct neurites: An immunocytochemical study of cultured rat cerebrum. J. Neurosci., 1987, 7(10), 3142-3153.
[http://dx.doi.org/10.1523/JNEUROSCI.07-10-03142.1987] [PMID: 2444675]
[14]
Harada, A.; Oguchi, K.; Okabe, S.; Kuno, J.; Terada, S.; Ohshima, T.; Sato-Yoshitake, R.; Takei, Y.; Noda, T.; Hirokawa, N. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature, 1994, 369(6480), 488-491.
[http://dx.doi.org/10.1038/369488a0] [PMID: 8202139]
[15]
Brandt, R.; Léger, J.; Lee, G. Interaction of tau with the neural plasma membrane mediated by tau’s amino-terminal projection domain. J. Cell Biol., 1995, 131(5), 1327-1340.
[http://dx.doi.org/10.1083/jcb.131.5.1327] [PMID: 8522593]
[16]
Brandt, R.; Leschik, J. Functional interactions of tau and their relevance for Alzheimer’s disease. Curr. Alzheimer Res., 2004, 1(4), 255-269.
[http://dx.doi.org/10.2174/1567205043332054] [PMID: 15975055]
[17]
Trushina, N.I.; Bakota, L.; Mulkidjanian, A.Y.; Brandt, R. The Evolution of Tau Phosphorylation and Interactions. Front. Aging Neurosci., 2019, 11, 256.
[http://dx.doi.org/10.3389/fnagi.2019.00256] [PMID: 31619983]
[18]
Janning, D.; Igaev, M.; Sündermann, F.; Brühmann, J.; Beutel, O.; Heinisch, J.J.; Bakota, L.; Piehler, J.; Junge, W.; Brandt, R. Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons. Mol. Biol. Cell, 2014, 25(22), 3541-3551.
[http://dx.doi.org/10.1091/mbc.e14-06-1099] [PMID: 25165145]
[19]
Niewidok, B.; Igaev, M.; Sündermann, F.; Janning, D.; Bakota, L.; Brandt, R. Presence of a carboxy-terminal pseudorepeat and disease-like pseudohyperphosphorylation critically influence tau’s interaction with microtubules in axon-like processes. Mol. Biol. Cell, 2016, 27(22), 3537-3549.
[http://dx.doi.org/10.1091/mbc.e16-06-0402] [PMID: 27582388]
[20]
Janke, C. The tubulin code: Molecular components, readout mechanisms, and functions. J. Cell Biol., 2014, 206(4), 461-472.
[http://dx.doi.org/10.1083/jcb.201406055] [PMID: 25135932]
[21]
Cash, A.D.; Aliev, G.; Siedlak, S.L.; Nunomura, A.; Fujioka, H.; Zhu, X.; Raina, A.K.; Vinters, H.V.; Tabaton, M.; Johnson, A.B.; Paula-Barbosa, M.; Avíla, J.; Jones, P.K.; Castellani, R.J.; Smith, M.A.; Perry, G. Microtubule reduction in Alzheimer’s disease and aging is independent of tau filament formation. Am. J. Pathol., 2003, 162(5), 1623-1627.
[http://dx.doi.org/10.1016/S0002-9440(10)64296-4] [PMID: 12707046]
[22]
Di Stefano, G.; Casoli, T.; Fattoretti, P.; Gracciotti, N.; Solazzi, M.; Bertoni-Freddari, C. Distribution of map2 in hippocampus and cerebellum of young and old rats by quantitative immunohistochemistry. J. Histochem. Cytochem., 2001, 49(8), 1065-1066.
[http://dx.doi.org/10.1177/002215540104900818] [PMID: 11457938]
[23]
Chauhan, N.; Siegel, G. Age-dependent organotypic expression of microtubule-associated proteins (MAP1, MAP2, and MAP5) in rat brain. Neurochem. Res., 1997, 22(6), 713-719.
[http://dx.doi.org/10.1023/A:1027306227402] [PMID: 9178955]
[24]
Braak, H.; Braak, E. Evolution of the neuropathology of Alzheimer’s disease. Acta Neurol. Scand. Suppl., 1996, 165, 3-12.
[http://dx.doi.org/10.1111/j.1600-0404.1996.tb05866.x] [PMID: 8740983]
[25]
Delacourte, A.; Flament, S.; Dibe, E.M.; Hublau, P.; Sablonnière, B.; Hémon, B.; Shérrer, V.; Défossez, A. Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer’s disease. Demonstration with a panel of antibodies against Tau proteins. Acta Neuropathol., 1990, 80(2), 111-117.
[http://dx.doi.org/10.1007/BF00308912] [PMID: 2117840]
[26]
Liu, W.K.; Dickson, D.W.; Yen, S.H. Heterogeneity of tau proteins in Alzheimer’s disease. Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites. Am. J. Pathol., 1993, 142(2), 387-394.
[PMID: 7679548]
[27]
Holzer, M.; Holzapfel, H.P.; Zedlick, D.; Brückner, M.K.; Arendt, T. Abnormally phosphorylated tau protein in Alzheimer’s disease: Heterogeneity of individual regional distribution and relationship to clinical severity. Neuroscience, 1994, 63(2), 499-516.
[http://dx.doi.org/10.1016/0306-4522(94)90546-0] [PMID: 7891861]
[28]
Probst, A.; Tolnay, M.; Langui, D.; Goedert, M.; Spillantini, M.G. Pick’s disease: Hyperphosphorylated tau protein segregates to the somatoaxonal compartment. Acta Neuropathol., 1996, 92(6), 588-596.
[http://dx.doi.org/10.1007/s004010050565] [PMID: 8960316]
[29]
Alquezar, C.; Arya, S.; Kao, A.W. Tau post-translational modifications: dynamic transformers of tau function, degradation, and aggregation. Front. Neurol., 2021, 11 ,595532.
[http://dx.doi.org/10.3389/fneur.2020.595532] [PMID: 33488497]
[30]
Tint, I.; Slaughter, T.; Fischer, I.; Black, M.M. Acute inactivation of tau has no effect on dynamics of microtubules in growing axons of cultured sympathetic neurons. J. Neurosci., 1998, 18(21), 8660-8673.
[http://dx.doi.org/10.1523/JNEUROSCI.18-21-08660.1998] [PMID: 9786973]
[31]
Lopes, S.; Vaz-Silva, J.; Pinto, V.; Dalla, C.; Kokras, N.; Bedenk, B.; Mack, N.; Czisch, M.; Almeida, O.F.; Sousa, N.; Sotiropoulos, I. Tau protein is essential for stress-induced brain pathology. Proc. Natl. Acad. Sci. USA, 2016, 113(26), E3755-E3763.
[http://dx.doi.org/10.1073/pnas.1600953113] [PMID: 27274066]
[32]
Tai, C.; Chang, C.W.; Yu, G.Q.; Lopez, I.; Yu, X.; Wang, X.; Guo, W.; Mucke, L. Tau reduction prevents key features of autism in mouse models. Neuron, 2020, 106(3), 421-437.e11.
[http://dx.doi.org/10.1016/j.neuron.2020.01.038] [PMID: 32126198]
[33]
Roberson, E.D.; Scearce-Levie, K.; Palop, J.J.; Yan, F.; Cheng, I.H.; Wu, T.; Gerstein, H.; Yu, G.Q.; Mucke, L. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science, 2007, 316(5825), 750-754.
[http://dx.doi.org/10.1126/science.1141736] [PMID: 17478722]
[34]
Selkoe, D.J.; Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med., 2016, 8(6), 595-608.
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[35]
Brandt, R.; Trushina, N.I.; Bakota, L. Much more than a cytoskeletal protein: Physiological and pathological functions of the non-microtubule binding region of tau. Front. Neurol., 2020, 11 ,590059.
[http://dx.doi.org/10.3389/fneur.2020.590059] [PMID: 33193056]
[36]
Uemura, N.; Uemura, M.T.; Luk, K.C.; Lee, V.M.; Trojanowski, J.Q. Cell-to-cell transmission of tau and α-synuclein. Trends Mol. Med., 2020, 26(10), 936-952.
[http://dx.doi.org/10.1016/j.molmed.2020.03.012] [PMID: 32371172]
[37]
Kfoury, N.; Holmes, B.B.; Jiang, H.; Holtzman, D.M.; Diamond, M.I. Trans-cellular propagation of Tau aggregation by fibrillar species. J. Biol. Chem., 2012, 287(23), 19440-19451.
[http://dx.doi.org/10.1074/jbc.M112.346072] [PMID: 22461630]
[38]
Takahashi, M.; Miyata, H.; Kametani, F.; Nonaka, T.; Akiyama, H.; Hisanaga, S.; Hasegawa, M. Extracellular association of APP and tau fibrils induces intracellular aggregate formation of tau. Acta Neuropathol., 2015, 129(6), 895-907.
[http://dx.doi.org/10.1007/s00401-015-1415-2] [PMID: 25869641]
[39]
Rauch, J.N.; Luna, G.; Guzman, E.; Audouard, M.; Challis, C.; Sibih, Y.E.; Leshuk, C.; Hernandez, I.; Wegmann, S.; Hyman, B.T.; Gradinaru, V.; Kampmann, M.; Kosik, K.S. LRP1 is a master regulator of tau uptake and spread. Nature, 2020, 580(7803), 381-385.
[http://dx.doi.org/10.1038/s41586-020-2156-5] [PMID: 32296178]
[40]
Vaquer-Alicea, J.; Diamond, M.I.; Joachimiak, L.A. Tau strains shape disease. Acta Neuropathol., 2021, 142(1), 57-71.
[http://dx.doi.org/10.1007/s00401-021-02301-7] [PMID: 33830330]
[41]
Altmann, K.H.; Wartmann, M.; O’Reilly, T. Epothilones and related structures-a new class of microtubule inhibitors with potent in vivo antitumor activity. Biochim. Biophys. Acta, 2000, 1470(3), M79-M91.
[PMID: 10799747]
[42]
Brunden, K.R.; Zhang, B.; Carroll, J.; Yao, Y.; Potuzak, J.S.; Hogan, A.M.; Iba, M.; James, M.J.; Xie, S.X.; Ballatore, C.; Smith, A.B., III; Lee, V.M.; Trojanowski, J.Q. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J. Neurosci., 2010, 30(41), 13861-13866.
[http://dx.doi.org/10.1523/JNEUROSCI.3059-10.2010] [PMID: 20943926]
[43]
Zhang, B.; Carroll, J.; Trojanowski, J.Q.; Yao, Y.; Iba, M.; Potuzak, J.S.; Hogan, A.M.; Xie, S.X.; Ballatore, C.; Smith, A.B., III; Lee, V.M.; Brunden, K.R. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J. Neurosci., 2012, 32(11), 3601-3611.
[http://dx.doi.org/10.1523/JNEUROSCI.4922-11.2012] [PMID: 22423084]
[44]
Barten, D.M.; Fanara, P.; Andorfer, C.; Hoque, N.; Wong, P.Y.; Husted, K.H.; Cadelina, G.W.; Decarr, L.B.; Yang, L.; Liu, V.; Fessler, C.; Protassio, J.; Riff, T.; Turner, H.; Janus, C.G.; Sankaranarayanan, S.; Polson, C.; Meredith, J.E.; Gray, G.; Hanna, A.; Olson, R.E.; Kim, S.H.; Vite, G.D.; Lee, F.Y.; Albright, C.F. Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau transgenic mice with low doses of the microtubule-stabilizing agent BMS-241027. J. Neurosci., 2012, 32(21), 7137-7145.
[http://dx.doi.org/10.1523/JNEUROSCI.0188-12.2012] [PMID: 22623658]
[45]
Chiorazzi, A.; Nicolini, G.; Canta, A.; Oggioni, N.; Rigolio, R.; Cossa, G.; Lombardi, R.; Roglio, I.; Cervellini, I.; Lauria, G.; Melcangi, R.C.; Bianchi, R.; Crippa, D.; Cavaletti, G. Experimental epothilone B neurotoxicity: Results of in vitro and in vivo studies. Neurobiol. Dis., 2009, 35(2), 270-277.
[http://dx.doi.org/10.1016/j.nbd.2009.05.006] [PMID: 19464369]
[46]
LaPointe, N.E.; Morfini, G.; Brady, S.T.; Feinstein, S.C.; Wilson, L.; Jordan, M.A. Effects of eribulin, vincristine, paclitaxel and ixabepilone on fast axonal transport and kinesin-1 driven microtubule gliding: Implications for chemotherapy-induced peripheral neuropathy. Neurotoxicology, 2013, 37, 231-239.
[http://dx.doi.org/10.1016/j.neuro.2013.05.008] [PMID: 23711742]
[47]
Clark, J.A.; Blizzard, C.A.; Breslin, M.C.; Yeaman, E.J.; Lee, K.M.; Chuckowree, J.A.; Dickson, T.C. Epothilone D accelerates disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Neuropathol. Appl. Neurobiol., 2018, 44(6), 590-605.
[http://dx.doi.org/10.1111/nan.12473] [PMID: 29380402]
[48]
Matsuoka, Y.; Jouroukhin, Y.; Gray, A.J.; Ma, L.; Hirata-Fukae, C.; Li, H.F.; Feng, L.; Lecanu, L.; Walker, B.R.; Planel, E.; Arancio, O.; Gozes, I.; Aisen, P.S. A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer’s disease. J. Pharmacol. Exp. Ther., 2008, 325(1), 146-153.
[http://dx.doi.org/10.1124/jpet.107.130526] [PMID: 18199809]
[49]
Ilschner, S.; Brandt, R. The transition of microglia to a ramified phenotype is associated with the formation of stable acetylated and detyrosinated microtubules. Glia, 1996, 18(2), 129-140.
[http://dx.doi.org/10.1002/(SICI)1098-1136(199610)18:2<129:AID-GLIA5>3.0.CO;2-W] [PMID: 8913776]
[50]
DeVos, S.L.; Miller, R.L.; Schoch, K.M.; Holmes, B.B.; Kebodeaux, C.S.; Wegener, A.J.; Chen, G.; Shen, T.; Tran, H.; Nichols, B.; Zanardi, T.A.; Kordasiewicz, H.B.; Swayze, E.E.; Bennett, C.F.; Diamond, M.I.; Miller, T.M. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci. Transl. Med., 2017, 9(374) ,eaag0481.
[http://dx.doi.org/10.1126/scitranslmed.aag0481] [PMID: 28123067]
[51]
Wischik, C.M.; Edwards, P.C.; Lai, R.Y.; Roth, M.; Harrington, C.R. Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc. Natl. Acad. Sci. USA, 1996, 93(20), 11213-11218.
[http://dx.doi.org/10.1073/pnas.93.20.11213] [PMID: 8855335]
[52]
Hochgräfe, K.; Sydow, A.; Matenia, D.; Cadinu, D.; Könen, S.; Petrova, O.; Pickhardt, M.; Goll, P.; Morellini, F.; Mandelkow, E.; Mandelkow, E.M. Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau. Acta Neuropathol. Commun., 2015, 3, 25.
[http://dx.doi.org/10.1186/s40478-015-0204-4] [PMID: 25958115]
[53]
Mendsaikhan, A.; Tooyama, I.; Bellier, J.P.; Serrano, G.E.; Sue, L.I.; Lue, L.F.; Beach, T.G.; Walker, D.G. Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer’s disease and aged brains: Increased levels correlate with neuropathology. Acta Neuropathol. Commun., 2019, 7(1), 215.
[http://dx.doi.org/10.1186/s40478-019-0862-8] [PMID: 31864418]
[54]
Kanmert, D.; Cantlon, A.; Muratore, C.R.; Jin, M.; O’Malley, T.T.; Lee, G.; Young-Pearse, T.L.; Selkoe, D.J.; Walsh, D.M. C-Terminally truncated forms of tau, but not full-length tau or its C-terminal fragments, are released from neurons independently of cell death. J. Neurosci., 2015, 35(30), 10851-10865.
[http://dx.doi.org/10.1523/JNEUROSCI.0387-15.2015] [PMID: 26224867]
[55]
Khatoon, S.; Grundke-Iqbal, I.; Iqbal, K. Levels of normal and abnormally phosphorylated tau in different cellular and regional compartments of Alzheimer disease and control brains. FEBS Lett., 1994, 351(1), 80-84.
[http://dx.doi.org/10.1016/0014-5793(94)00829-9] [PMID: 8076698]
[56]
Sunderland, T.; Linker, G.; Mirza, N.; Putnam, K.T.; Friedman, D.L.; Kimmel, L.H.; Bergeson, J.; Manetti, G.J.; Zimmermann, M.; Tang, B.; Bartko, J.J.; Cohen, R.M. Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA, 2003, 289(16), 2094-2103.
[http://dx.doi.org/10.1001/jama.289.16.2094] [PMID: 12709467]
[57]
Han, P.; Serrano, G.; Beach, T.G.; Caselli, R.J.; Yin, J.; Zhuang, N.; Shi, J. A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor. J. Neuropathol. Exp. Neurol., 2017, 76(1), 44-51.
[http://dx.doi.org/10.1093/jnen/nlw105] [PMID: 28069930]
[58]
Collin, L.; Bohrmann, B.; Göpfert, U.; Oroszlan-Szovik, K.; Ozmen, L.; Grüninger, F. Neuronal uptake of tau/pS422 antibody and reduced progression of tau pathology in a mouse model of Alzheimer’s disease. Brain, 2014, 137(Pt 10), 2834-2846.
[http://dx.doi.org/10.1093/brain/awu213] [PMID: 25085375]
[59]
Congdon, E.E.; Gu, J.; Sait, H.B.; Sigurdsson, E.M. Antibody uptake into neurons occurs primarily via clathrin-dependent Fcγ receptor endocytosis and is a prerequisite for acute tau protein clearance. J. Biol. Chem., 2013, 288(49), 35452-35465.
[http://dx.doi.org/10.1074/jbc.M113.491001] [PMID: 24163366]
[60]
Gu, J.; Congdon, E.E.; Sigurdsson, E.M. Two novel Tau antibodies targeting the 396/404 region are primarily taken up by neurons and reduce Tau protein pathology. J. Biol. Chem., 2013, 288(46), 33081-33095.
[http://dx.doi.org/10.1074/jbc.M113.494922] [PMID: 24089520]
[61]
Congdon, E.E.; Chukwu, J.E.; Shamir, D.B.; Deng, J.; Ujla, D.; Sait, H.B.R.; Neubert, T.A.; Kong, X.P.; Sigurdsson, E.M. Tau antibody chimerization alters its charge and binding, thereby reducing its cellular uptake and efficacy. EBioMedicine, 2019, 42, 157-173.
[http://dx.doi.org/10.1016/j.ebiom.2019.03.033] [PMID: 30910484]
[62]
Arendt, T.; Stieler, J.T.; Holzer, M. Tau and tauopathies. Brain Res. Bull., 2016, 126(Pt 3), 238-292.
[http://dx.doi.org/10.1016/j.brainresbull.2016.08.018] [PMID: 27615390]
[63]
Maas, T.; Eidenmüller, J.; Brandt, R. Interaction of tau with the neural membrane cortex is regulated by phosphorylation at sites that are modified in paired helical filaments. J. Biol. Chem., 2000, 275(21), 15733-15740.
[http://dx.doi.org/10.1074/jbc.M000389200] [PMID: 10747907]
[64]
Serenó, L.; Coma, M.; Rodríguez, M.; Sánchez-Ferrer, P.; Sánchez, M.B.; Gich, I.; Agulló, J.M.; Pérez, M.; Avila, J.; Guardia-Laguarta, C.; Clarimón, J.; Lleó, A.; Gómez-Isla, T. A novel GSK-3beta inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol. Dis., 2009, 35(3), 359-367.
[http://dx.doi.org/10.1016/j.nbd.2009.05.025] [PMID: 19523516]
[65]
Yuzwa, S.A.; Shan, X.; Macauley, M.S.; Clark, T.; Skorobogatko, Y.; Vosseller, K.; Vocadlo, D.J. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat. Chem. Biol., 2012, 8(4), 393-399.
[http://dx.doi.org/10.1038/nchembio.797] [PMID: 22366723]
[66]
Graham, D.L.; Gray, A.J.; Joyce, J.A.; Yu, D.; O’Moore, J.; Carlson, G.A.; Shearman, M.S.; Dellovade, T.L.; Hering, H. Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy. Neuropharmacology, 2014, 79, 307-313.
[http://dx.doi.org/10.1016/j.neuropharm.2013.11.025] [PMID: 24326295]
[67]
Matsuoka, Y.; Gray, A.J.; Hirata-Fukae, C.; Minami, S.S.; Waterhouse, E.G.; Mattson, M.P.; LaFerla, F.M.; Gozes, I.; Aisen, P.S. Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer’s disease at early pathological stage. J. Mol. Neurosci., 2007, 31(2), 165-170.
[PMID: 17478890]
[68]
Tackenberg, C.; Brandt, R. Divergent pathways mediate spine alterations and cell death induced by amyloid-beta, wild-type tau, and R406W tau. J. Neurosci., 2009, 29(46), 14439-14450.
[http://dx.doi.org/10.1523/JNEUROSCI.3590-09.2009] [PMID: 19923278]
[69]
Zakaria, A.; Hamdi, N.; Abdel-Kader, R.M. Methylene blue improves brain Mitochondrial ABAD Functions and Decreases Aβ in a Neuroinflammatory Alzheimer’s Disease Mouse Model. Mol. Neurobiol., 2016, 53(2), 1220-1228.
[http://dx.doi.org/10.1007/s12035-014-9088-8] [PMID: 25601181]
[70]
Necula, M.; Breydo, L.; Milton, S.; Kayed, R.; van der Veer, W.E.; Tone, P.; Glabe, C.G. Methylene blue inhibits amyloid Abeta oligomerization by promoting fibrillization. Biochemistry, 2007, 46(30), 8850-8860.
[http://dx.doi.org/10.1021/bi700411k] [PMID: 17595112]
[71]
Llorens-Martín, M.; Jurado, J.; Hernández, F.; Avila, J. GSK-3β, a pivotal kinase in Alzheimer disease. Front. Mol. Neurosci., 2014, 7, 46.
[PMID: 24904272]
[72]
Ostrowski, A.; van Aalten, D.M. Chemical tools to probe cellular O-GlcNAc signalling. Biochem. J., 2013, 456(1), 1-12.
[http://dx.doi.org/10.1042/BJ20131081] [PMID: 24156473]
[73]
de Queiroz, R.M.; Carvalho, E.; Dias, W.B. O-GlcNAcylation: The sweet side of the cancer. Front. Oncol., 2014, 4, 132.
[http://dx.doi.org/10.3389/fonc.2014.00132] [PMID: 24918087]
[74]
Golovyashkina, N.; Penazzi, L.; Ballatore, C.; Smith, A.B., III; Bakota, L.; Brandt, R. Region-specific dendritic simplification induced by Aβ, mediated by tau via dysregulation of microtubule dynamics: A mechanistic distinct event from other neurodegenerative processes. Mol. Neurodegener., 2015, 10, 60.
[http://dx.doi.org/10.1186/s13024-015-0049-0] [PMID: 26541821]
[75]
Davis, E.J.; Foster, T.D.; Thomas, W.E. Cellular forms and functions of brain microglia. Brain Res. Bull., 1994, 34(1), 73-78.
[http://dx.doi.org/10.1016/0361-9230(94)90189-9] [PMID: 8193937]
[76]
Mao, L.; Gao, W.; Chen, S.; Song, Y.; Song, C.; Zhou, Z.; Zhao, H.; Zhou, K.; Wang, W.; Zhu, K.; Liu, C.; Mei, X. Epothilone B impairs functional recovery after spinal cord injury by increasing secretion of macrophage colony-stimulating factor. Cell Death Dis., 2017, 8(11) ,e3162.
[http://dx.doi.org/10.1038/cddis.2017.542] [PMID: 29095439]
[77]
Fath, T.; Eidenmüller, J.; Brandt, R. Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer’s disease. J. Neurosci., 2002, 22(22), 9733-9741.
[http://dx.doi.org/10.1523/JNEUROSCI.22-22-09733.2002] [PMID: 12427828]
[78]
Gerson, J.; Castillo-Carranza, D.L.; Sengupta, U.; Bodani, R.; Prough, D.S.; DeWitt, D.S.; Hawkins, B.E.; Kayed, R. Tau oligomers derived from traumatic brain injury cause cognitive impairment and accelerate onset of pathology in htau mice. J. Neurotrauma, 2016, 33(22), 2034-2043.
[http://dx.doi.org/10.1089/neu.2015.4262] [PMID: 26729399]
[79]
Kopeikina, K.J.; Hyman, B.T.; Spires-Jones, T.L. Soluble forms of tau are toxic in Alzheimer’s disease. Transl. Neurosci., 2012, 3(3), 223-233.
[http://dx.doi.org/10.2478/s13380-012-0032-y] [PMID: 23029602]
[80]
Plouffe, V.; Mohamed, N.V.; Rivest-McGraw, J.; Bertrand, J.; Lauzon, M.; Leclerc, N. Hyperphosphorylation and cleavage at D421 enhance tau secretion. PLoS One, 2012, 7(5) ,e36873.
[http://dx.doi.org/10.1371/journal.pone.0036873] [PMID: 22615831]
[81]
Sündermann, F.; Fernandez, M.P.; Morgan, R.O. An evolutionary roadmap to the microtubule-associated protein MAP Tau. BMC Genomics, 2016, 17, 264.
[http://dx.doi.org/10.1186/s12864-016-2590-9] [PMID: 27030133]
[82]
Bechstedt, S.; Lu, K.; Brouhard, G.J. Doublecortin recognizes the longitudinal curvature of the microtubule end and lattice. Curr. Biol., 2014, 24(20), 2366-2375.
[http://dx.doi.org/10.1016/j.cub.2014.08.039] [PMID: 25283777]
[83]
Samsonov, A.; Yu, J.Z.; Rasenick, M.; Popov, S.V. Tau interaction with microtubules in vivo. J. Cell Sci., 2004, 117(Pt 25), 6129-6141.
[http://dx.doi.org/10.1242/jcs.01531] [PMID: 15564376]
[84]
Guillaud, L.; Bosc, C.; Fourest-Lieuvin, A.; Denarier, E.; Pirollet, F.; Lafanechère, L.; Job, D. STOP proteins are responsible for the high degree of microtubule stabilization observed in neuronal cells. J. Cell Biol., 1998, 142(1), 167-179.
[http://dx.doi.org/10.1083/jcb.142.1.167] [PMID: 9660871]
[85]
Slaughter, T.; Black, M.M. STOP (stable-tubule-only-polypeptide) is preferentially associated with the stable domain of axonal microtubules. J. Neurocytol., 2003, 32(4), 399-413.
[http://dx.doi.org/10.1023/B:NEUR.0000011334.70648.87] [PMID: 14724383]
[86]
Tortosa, E.; Adolfs, Y.; Fukata, M.; Pasterkamp, R.J.; Kapitein, L.C.; Hoogenraad, C.C. Dynamic Palmitoylation Targets MAP6 to the axon to promote microtubule stabilization during neuronal polarization. Neuron, 2017, 94(4), 809-825.e7.
[http://dx.doi.org/10.1016/j.neuron.2017.04.042] [PMID: 28521134]
[87]
Liedtke, W.; Leman, E.E.; Fyffe, R.E.; Raine, C.S.; Schubart, U.K. Stathmin-deficient mice develop an age-dependent axonopathy of the central and peripheral nervous systems. Am. J. Pathol., 2002, 160(2), 469-480.
[http://dx.doi.org/10.1016/S0002-9440(10)64866-3] [PMID: 11839567]
[88]
Hamilton, E.M.; Polder, E.; Vanderver, A.; Naidu, S.; Schiffmann, R.; Fisher, K.; Raguž, A.B.; Blumkin, L.; van Berkel, C.G.; Waisfisz, Q.; Simons, C.; Taft, R.J.; Abbink, T.E.; Wolf, N.I.; van der Knaap, M.S. Hypomyelination with atrophy of the basal ganglia and cerebellum: Further delineation of the phenotype and genotype-phenotype correlation. Brain, 2014, 137(Pt 7), 1921-1930.
[http://dx.doi.org/10.1093/brain/awu110] [PMID: 24785942]
[89]
Nicita, F.; Bertini, E.; Travaglini, L.; Armando, M.; Aiello, C. Congenital-onset spastic paraplegia in a patient with TUBB4A mutation and mild hypomyelination. J. Neurol. Sci., 2016, 368, 145-146.
[http://dx.doi.org/10.1016/j.jns.2016.07.002] [PMID: 27538619]
[90]
Bahi-Buisson, N.; Poirier, K.; Fourniol, F.; Saillour, Y.; Valence, S.; Lebrun, N.; Hully, M.; Bianco, C.F.; Boddaert, N.; Elie, C.; Lascelles, K.; Souville, I.; Beldjord, C.; Chelly, J. The wide spectrum of tubulinopathies: What are the key features for the diagnosis? Brain, 2014, 137(Pt 6), 1676-1700.
[http://dx.doi.org/10.1093/brain/awu082] [PMID: 24860126]
[91]
d’Ydewalle, C.; Krishnan, J.; Chiheb, D.M.; Van Damme, P.; Irobi, J.; Kozikowski, A.P.; Vanden Berghe, P.; Timmerman, V.; Robberecht, W.; Van Den Bosch, L. HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. Nat. Med., 2011, 17(8), 968-974.
[http://dx.doi.org/10.1038/nm.2396] [PMID: 21785432]
[92]
Hempen, B.; Brion, J.P. Reduction of acetylated alpha-tubulin immunoreactivity in neurofibrillary tangle-bearing neurons in Alzheimer’s disease. J. Neuropathol. Exp. Neurol., 1996, 55(9), 964-972.
[http://dx.doi.org/10.1097/00005072-199609000-00003] [PMID: 8800092]
[93]
Dompierre, J.P.; Godin, J.D.; Charrin, B.C.; Cordelières, F.P.; King, S.J.; Humbert, S.; Saudou, F. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. J. Neurosci., 2007, 27(13), 3571-3583.
[http://dx.doi.org/10.1523/JNEUROSCI.0037-07.2007] [PMID: 17392473]
[94]
Vu, H.T.; Akatsu, H.; Hashizume, Y.; Setou, M.; Ikegami, K. Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer’s disease. Sci. Rep., 2017, 7, 40205.
[http://dx.doi.org/10.1038/srep40205] [PMID: 28067280]
[95]
Zhang, F.; Su, B.; Wang, C.; Siedlak, S.L.; Mondragon-Rodriguez, S.; Lee, H.G.; Wang, X.; Perry, G.; Zhu, X. Posttranslational modifications of α-tubulin in Alzheimer disease. Transl. Neurodegener., 2015, 4, 9.
[http://dx.doi.org/10.1186/s40035-015-0030-4] [PMID: 26029362]
[96]
Pagnamenta, A.T.; Heemeryck, P.; Martin, H.C.; Bosc, C.; Peris, L.; Uszynski, I.; Gory-Fauré, S.; Couly, S.; Deshpande, C.; Siddiqui, A.; Elmonairy, A.A.; Jayawant, S.; Murthy, S.; Walker, I.; Loong, L.; Bauer, P.; Vossier, F.; Denarier, E.; Maurice, T.; Barbier, E.L.; Deloulme, J.C.; Taylor, J.C.; Blair, E.M.; Andrieux, A.; Moutin, M.J. Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice. Hum. Mol. Genet., 2019, 28(20), 3391-3405.
[http://dx.doi.org/10.1093/hmg/ddz186] [PMID: 31363758]
[97]
Prezel, E.; Elie, A.; Delaroche, J.; Stoppin-Mellet, V.; Bosc, C.; Serre, L.; Fourest-Lieuvin, A.; Andrieux, A.; Vantard, M.; Arnal, I. Tau can switch microtubule network organizations: From random networks to dynamic and stable bundles. Mol. Biol. Cell, 2018, 29(2), 154-165.
[http://dx.doi.org/10.1091/mbc.E17-06-0429] [PMID: 29167379]
[98]
Zempel, H.; Mandelkow, E.M. Tau missorting and spastin-induced microtubule disruption in neurodegeneration. Alzheimer Disease and Hereditary Spastic Paraplegia. Mol. Neurodegener., 2015, 10, 68.
[http://dx.doi.org/10.1186/s13024-015-0064-1] [PMID: 26691836]
[99]
Ren, Y.; Zhao, J.; Feng, J. Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation. J. Neurosci., 2003, 23(8), 3316-3324.
[http://dx.doi.org/10.1523/JNEUROSCI.23-08-03316.2003] [PMID: 12716939]
[100]
Law, B.M.; Spain, V.A.; Leinster, V.H.; Chia, R.; Beilina, A.; Cho, H.J.; Taymans, J.M.; Urban, M.K.; Sancho, R.M.; Blanca, R.M.; Biskup, S.; Baekelandt, V.; Cai, H.; Cookson, M.R.; Berwick, D.C.; Harvey, K. A direct interaction between leucine-rich repeat kinase 2 and specific β-tubulin isoforms regulates tubulin acetylation. J. Biol. Chem., 2014, 289(2), 895-908.
[http://dx.doi.org/10.1074/jbc.M113.507913] [PMID: 24275654]

Rights & Permissions Print Cite
Article Metrics
47
1
© 2024 Bentham Science Publishers | Privacy Policy