Abstract
Tau is a microtubule-associated binding protein in the nervous system that is known for its role in stabilizing microtubules throughout the nerve cell. It accumulates as β-sheet-rich aggregates and neurofibrillary tangles, leading to an array of different pathologies. Six splice variants of this protein, generated from the microtubule-associated protein tau (MAPT) gene, are expressed in the brain. Amongst these variants, 0N3R, is prominent during fetal development, while the rest, 0N4R, 1N3R, 1N4R, 2N3R, and 2N4R, are expressed in postnatal stages. Tau isoforms play their role separately or in combination with others to contribute to one or multiple neurodegenerative disorders and clinical syndromes. For instance, in Alzheimer’s disease and a subset of frontotemporal lobar degeneration (FTLD)-MAPT (i.e., R406W and V337M), both 3R and 4R isoforms are involved; therefore, they are called 3R/4R mix tauopathies. On the other hand, 4R isoforms are aggregated in progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and a majority of FTLD-MAPT and these diseases are called 4R tauopathies. Similarly, Pick’s disease has an association with 3R tau isoforms and is thereby referred to as 3R tauopathy. Unlike 3R isoforms, the 4R variants have a faster rate of aggregation that accelerates the associated neurodegenerative mechanisms. Moreover, post-translational modifications of each isoform occur at a different rate and dictate their physiological and pathological attributes. The smallest tau isoform (0N3R) is highly phosphorylated in the fetal brain but does not lead to the generation of aggregates. On the other hand, proteoforms in the adult human brain undergo aggregation upon their phosphorylation and glycation. Expanding on this knowledge, this article aims to review the physiological and pathological roles of tau isoforms and their underlying mechanisms that result in neurological deficits.
Graphical Abstract
Physiological and pathological relevance of microtubule-associated protein tau (MAPT): Tau exists as six splice variants in the brain, each differing with respect to expression, post-translational modifications (PTMs), and aggregation kinetics. Physiologically, they are involved in the stabilization of microtubules that form the molecular highways for axonal transport. However, an imbalance in their expression and the associated PTMs leads to a disruption in their physiological function through the formation of neurofibrillary tangles that accumulate in various regions of the brain and contribute to several types of tauopathies.
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References
Goedert M, Eisenberg DS, Crowther RA (2017) Propagation of tau aggregates and neurodegeneration. Annu Rev Neurosci 40(1):189–210. https://doi.org/10.1146/annurev-neuro-072116-031153
Roesler TW, Marvian AT, Brendel M, Nykaenen NP, Hoellerhage M, Schwarz SC, Hopfner F, Koeglsperger T, et al (2019) Four-repeat tauopathies. Prog neurobiol 180:101644. https://doi.org/10.1016/j.pneurobio.2019.101644
Shi Y, Zhang W, Yang Y, Murzin AG, Falcon B, Kotecha A, van Beers M, Tarutani A, et al (2021) Structure-based classification of tauopathies. Nature 598(7880):359–363. https://doi.org/10.1038/s41586-021-03911-7
Franzmeier N, Brendel M, Beyer L, Slemann L, Kovacs GG, Arzberger T, Kurz C, Respondek G, et al (2022) Tau deposition patterns are associated with functional connectivity in primary tauopathies. Nat Comm 13(1):1362. https://doi.org/10.1038/s41467-022-28896-3
Caillet-Boudin ML, Fernandez-Gomez FJ, Tran H, Dhaenens CM, Buee L, Sergeant N (2014) Brain pathology in myotonic dystrophy: when tauopathy meets spliceopathy and RNAopathy. Front Mol Neuro 6:57. https://doi.org/10.3389/fnmol.2013.00057
Hook V, Boyarko B (2021) Human tau isoforms and proteolysis for production of toxic tau fragments in neurodegeneration. Front Neurosci 15:702788. https://doi.org/10.3389/fnins.2021.702788
Barbier P, Zejneli O, Martinho M et al (2019) Role of tau as a microtubule-associated protein: structural and functional aspects. Front Aging Neurosci 11:204. https://doi.org/10.3389/fnagi.2019.00204
Eidenmuller J, Fath T, Maas T, Pool M, Sontag E, Brandt R (2001) Phosphorylation-mimicking glutamate clusters in the proline-rich region are sufficient to simulate the functional deficiencies of hyperphosphorylated tau protein. Biochem J 357(3):759–767. https://doi.org/10.1042/0264-6021:3570759
Feijoo C, Campbell DG, Jakes R, Goedert M, Cuenda A (2005) Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38 at Thr50 promotes microtubule assembly. J Cell Sci 118(2):397–408. https://doi.org/10.1242/jcs.01655
Morris CE, Wang JA, Markin VS (2003) The invagination of excess surface area by shrinking neurons. Biophys J 85(1):223–235. https://doi.org/10.1016/S0006-3495(03)74468-3
Goedert M, Spillantini MG (2011) Pathogenesis of the tauopathies. J Mol Neurosci 45(3):425–431. https://doi.org/10.1007/s12031-011-9593-4
Qi Z, Erin EC, Haikady NN, Jeff K (2012) Tau isoform composition influences rate and extent of filament formation. J Bio Chem 287(24):20711–20719. https://doi.org/10.1074/jbc.M112.364067
Mandelkow EM, Mandelkow E (2012) Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med 2(7):a006247. https://doi.org/10.1101/cshperspect.a006247
Yoshida M (2006) Cellular tau pathology and immunohistochemical study of tau isoforms in sporadic tauopathies. Neuropathol 26(5):457–470. https://doi.org/10.1111/j.1440-1789.2006.00743.x
Huin V, Buee L, Behal H et al (2017) Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer’s disease and progressive supranuclear palsy brains. Sci Rep 7(1):1–10. https://doi.org/10.1038/s41598-017-12955-7
Liu Q, Fang L, Wu C (2022) Alternative splicing and isoforms: from mechanisms to diseases. Genes 13:3–401. https://doi.org/10.3390/genes13030401
Coupland KG, Kim WS, Halliday GM, Hallupp M, Dobson-Stone C, Kwok JB (2016) Role of the long non-coding RNA MAPT-AS1 in regulation of microtubule associated protein tau (MAPT) expression in Parkinson’s disease. PLoS One 11:6-e0157924. https://doi.org/10.1371/journal.pone.0157924
Lan Z, Chen Y, Jin J, Xu Y, Zhu X (2021) Long non-coding RNA: insight into mechanisms of Alzheimer’s disease. Front Mol Neurosci 14. https://doi.org/10.3389/fnmol.2021.821002
Caillet-Boudin ML, Buee L, Sergeant N, Lefebvre B (2015) Regulation of human MAPT gene expression. Mol Neurodegener 10:28. https://doi.org/10.1186/s13024-015-0025-8
Fischer I (2022) Evolutionary perspective of Big tau structure: 4a exon variants of MAPT. Front Mol Neurosci 15:1019999. https://doi.org/10.3389/fnmol.2022.1019999
Couchie D, Mavilia C, Georgieff IS, Liem RK, Shelanski ML, Nunez J (1992) Primary structure of high molecular weight tau present in the peripheral nervous system. Proc Natl Acad 89(10):4378–4381. https://doi.org/10.1073/pnas.89.10.4378
Andreadis A (2005) Tau gene alternative splicing: expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases. Biochem Biophys acta 1739(2–3):91–103. https://doi.org/10.1016/j.bbadis.2004.08.010
Medina M, Hernendez F, Avila J (2016) New features about tau function and dysfunction. Biomolecules 6:2–21. https://doi.org/10.3390/biom6020021
Ruiz-Gabarre D, Carnero-Espejo A, Åvila J, Garcia-Escudero V (2022) What’s in a gene? The outstanding diversity of MAPT. Cells 11:5–840. https://doi.org/10.3390/cells11050840
Garcia-Escudero V, Ruiz-Gabarre D, Gargini R, Perez M et al (2021) A new non-aggregative splicing isoform of human Tau is decreased in Alzheimer’s disease. Acta Neuropathol 142(1):159–177. https://doi.org/10.1007/s00401-021-02317-z
Rawat P, Sehar U, Bisht J, Selman A, Culberson J, Reddy PH (2022) Phosphorylated tau in Alzheimer’s disease and other tauopathies. Int J Mol Sci 23(21):12841. https://doi.org/10.3390/ijms232112841
Ngian ZK, Tan YY, Choo CT, Lin WQ et al (2022) Truncated Tau caused by intron retention is enriched in Alzheimer’s disease cortex and exhibits altered biochemical properties. Proc Natl Acad 119:37-e2204179119. https://doi.org/10.1073/pnas.2204179119
Wang ZH, Liu P, Liu X, Yu SP, Wang JZ, Ye K (2018) Delta-secretase (AEP) mediates tau-splicing imbalance and accelerates cognitive decline in tauopathies. J Exp Med 215(12):3038–3056. https://doi.org/10.1084/jem.20180539
Gamblin TC, Chen F, Zambrano A et al (2003) Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer’s disease. PNAS 100(17):10032–10037. https://doi.org/10.1073/pnas.1630428100
Friedrich MG, Skora A, Hancock SE, Mitchell TW, Else PL, Truscott RJ (2021) Tau is truncated in five regions of the normal adult human brain. Int J Mol Sci 22(7):3521. https://doi.org/10.3390/ijms22073521
Stewart M (2019) Polyadenylation and nuclear export of mRNAs. J Biol Chem 294(9):2977–2987. https://doi.org/10.1074/jbc.REV118.005594
Montalbano M, Jaworski E, Garcia S, Ellsworth A, McAllen S, Routh A, Kayed R (2021) Tau modulates mrna transcription, alternative polyadenylation profiles of hnRNPs, chromatin remodeling and spliceosome complexes. Front Mol Neurosci 14:742790. https://doi.org/10.3389/fnmol.2021.742790
Papegaey A, Eddarkaoui S, Deramecourt V et al (2016) Reduced Tau protein expression is associated with frontotemporal degeneration with progranulin mutation. Acta Neuropathol Commun 4(1):74. https://doi.org/10.1186/s40478-016-0345-0
Ward ME, Miller BL (2011) Potential mechanisms of progranulin-deficient FTLD. J Mol Neurosci 45(3):574–582. https://doi.org/10.1007/s12031-011-9622-3
Hefti MM, Farrell K, Kim S, Bowles KR, Fowkes ME, Raj T, Crary JF (2018) High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development. PloS one 13(4):e0195771. https://doi.org/10.1371/journal.pone.0195771
Bachmann S, Bell M, Klimek J, Zempel H (2021) Differential effects of the six human TAU isoforms: Somatic retention of 2N-TAU and increased microtubule number induced by 4R-TAU. Front Neurosci 15:643115. https://doi.org/10.3389/fnins.2021.643115
Scheres SH, Zhang W, Falcon B, Goedert M (2020) Cryo-EM structures of tau filaments. Curr Opin Struct Biol 64:17–25. https://doi.org/10.1016/j.sbi.2020.05.011
Fitzpatrick AW, Falcon B, He S et al (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547(7662):185–190. https://doi.org/10.1038/nature23002
Trabzuni D, Wray S, Vandrovcova J, Ramasamy A, Walker R, Smith C, Ryten M (2012) MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies. Hum Mol Genet 21(18):4094–4103. https://doi.org/10.1093/hmg/dds238
Bell M, Zempel H (2022) SH-SY5Y-derived neurons: a human neuronal model system for investigating TAU sorting and neuronal subtype-specific TAU vulnerability. Rev Neurosci 33(1):1–15. https://doi.org/10.1515/revneuro-2020-0152
Li L, Xu ZP, Liu GP, Xu C, Wang ZH, Li XG, Wang JZ (2015) Expression of 1N3R-Tau isoform inhibits cell proliferation by inducing S phase arrest in N2a cells. PLoS One 10(3). https://doi.org/10.1371/journal.pone.0119865
Sinadinos C, Cowan CM, Wyttenbach A, Mudher A (2012) Increased throughput assays of locomotor dysfunction in Drosophila larvae. J Neurosci Methods 203(2):325–334. https://doi.org/10.1016/j.jneumeth.2011.08.037
Sealey MA, Vourkou E, Cowan CM, Bossing T, Quraishe S, Grammenoudi S, Mudher A (2017) Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic model of tauopathy. Neurobiol Dis 105:74–83. https://doi.org/10.1016/j.nbd.2017.05.003
Williams DW, Tyrer M, Shepherd D (2000) Tau and tau reporters disrupt central projections of sensory neurons in Drosophila. J Comp Neurol 428(4):630–640. https://doi.org/10.1002/1096-9861(20001225)428:4%3c630::aid-cne4%3e3.0.co;2-x
Nishimura I, Yang Y, Lu B (2004) PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell 116(5):671–682. https://doi.org/10.1016/s0092-8674(04)00170-9
Pampuscenko K, Morkuniene R, Sneideris T, Smirnovas V, Budvytyte R, Valincius G, Borutaite V (2020) Extracellular tau induces microglial phagocytosis of living neurons in cell cultures. J Neurochem 154(3):316–329. https://doi.org/10.1111/jnc.14940
Pampuscenko K, Morkuniene R, Krasauskas L, Smirnovas V, Tomita T, Borutaite V (2021) Distinct neurotoxic effects of extracellular tau species in primary neuronal-glial cultures. Mol Neurobiol 58(2):658–667. https://doi.org/10.1007/s12035-020-02150-7
Mah L, Binns MA, Steffens DC (2015) Alzheimer’s Disease Neuroimaging Initiative Anxiety symptoms in amnestic mild cognitive impairment are associated with medial temporal atrophy and predict conversion to Alzheimer disease. Am J Geriatr. Psychiatry 23(5):466–476. https://doi.org/10.1016/j.jagp.2014.10.005
Geda YE, Roberts RO, Mielke MM, Knopman DS, Christianson TJ, Pankratz VS, Rocca WA (2014) Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study. Am J Psychiatry 171(5):572–581. https://doi.org/10.1176/appi.ajp.2014.13060821
Marciniak E, Leboucher A, Caron E, Ahmed T, Tailleux A, Dumont J, Blum D (2017) Tau deletion promotes brain insulin resistance. J Exp Med 214(8):2257–2269. https://doi.org/10.1084/jem.20161731
Wijesekara N, Goncalves RA, Ahrens R, De Felice FG, Fraser PE (2018) Tau ablation in mice leads to pancreatic cell dysfunction and glucose intolerance. FASEB J 32(6):3166–3173. https://doi.org/10.1096/fj.201701352
Lei P, Ayton S, Moon S, Zhang Q, Volitakis I, Finkelstein DI, Bush AI (2014) Motor and cognitive deficits in aged tau knockout mice in two background strains. Mol Neurodegener 9(1):1–12. https://doi.org/10.1186/1750-1326-9-29
Rebolledo-Solleiro D, Roldan-Roldan G, Diaz D, Velasco M, Larque C, Rico-Rosillo G, Perez de la Mora M (2017) Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats. PLoS One 12(5). https://doi.org/10.1371/journal.pone.0176554
Biallosterski BT, Prickaerts J, Rahnama’i MS, De Wachter S, Van Koeveringe GA, Meriaux C (2015) Changes in voiding behavior in a mouse model of Alzheimer’s disease. Front Aging Neurosci 7:160. https://doi.org/10.3389/fnagi.2015.00160
Mendez MF (2021) The relationship between anxiety and Alzheimer’s disease. J Alzheimers Dis Rep 5(1):171–177. https://doi.org/10.3233/ADR-210294
Gonßalves RA, Wijesekara N, Fraser PE, De Felice FG (2020) Behavioral abnormalities in knockout and humanized tau mice. Front endocrinol 11:124. https://doi.org/10.3389/fendo.2020.00124
Wheeler JM, McMillan PJ, Hawk M (2015) High copy wildtype human 1N4R tau expression promotes early pathological tauopathy accompanied by cognitive deficits without progressive neurofibrillary degeneration. Acta Neuropathol Commun 3:33. https://doi.org/10.1186/s40478-015-0210-6
Sun Y, Guo Y, Feng X, Jia M, Ai N, Dong Y, Kong W (2020) The behavioral and neuropathologic sexual dimorphism and absence of MIP-3 in tau P301S mouse model of Alzheimer’s disease. J Neuroinflammation 17(1):1–18. https://doi.org/10.1186/s12974-020-01749-w
Flavin WP, Bousset L, Green ZC, Chu Y, Skarpathiotis S, Chaney MJ, Campbell EM (2017) Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins. Acta Neuropathol 134(4):629–653. https://doi.org/10.1007/s00401-017-1722-x
Wu L, Wang Z, Ladd S, Dougharty DT, Madhavan SS, Marcus M, Xu B (2020) Human tau isoform aggregation and selective detection of misfolded tau from post-mortem Alzheimer’s disease brains. bioRxiv, 2019–12. https://doi.org/10.1101/2019.12.31.876946
Tennant JM, Henderson DM, Wisniewski TM, Hoover EA (2020) RT-QuIC detection of tauopathies using full-length tau substrates. Prion 14(1):249–256. https://doi.org/10.1080/19336896.2020.1832946
Kim SH, Farrell K, Cosentino S et al (2021) Tau isoform profile in essential tremor diverges from other tauopathies. J Neuropathol Exp 80(9):835–843. https://doi.org/10.1093/jnen/nlab073
Gong CX, Liu F, Grundke-Iqbal I, Iqbal K (2005) Post-translational modifications of tau protein in Alzheimer’s disease. J Neural Transm 112(6):813–838. https://doi.org/10.1007/s00702-004-0221-0
Wang Y, Mandelkow E (2016) Tau in physiology and pathology. Nat Rev Neurosci 17(1):22–35. https://doi.org/10.1038/nrn.2015.1
Wesseling H, Mair W, Kumar M et al (2020) Tau PTM profiles identify patient heterogeneity and stages of Alzheimer’s disease. Cell 183(6):1699–1713. https://doi.org/10.1016/j.cell.2020.10.029
Boxer AL, Polydoro M (2020) Targeting tau: clinical trials and novel therapeutic approaches. Neurosci Lett 731. https://doi.org/10.1016/j.neulet.2020.134919
Cho SH, Zhou Y, Schroeder S, Haroutunian V, Seeley WW, Gan L (2010) Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 67(6):953–966. https://doi.org/10.1016/j.neuron.2010.08.044
Cohen TJ, Guo JL, Hurtado DE, Kwong LK, Mills IP, Trojanowski JQ, Lee VM (2011) The acetylation of tau inhibits its function and promotes pathological tau aggregation. Nat Commun 2(1):1–9. https://doi.org/10.1038/ncomms1255
Goedert M, Jakes R, Crowther RA, Six J, Lbke U, Vandermeeren M, Lee VM (1993) The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development. PNAS 90(11):5066–5070. https://doi.org/10.1073/pnas.90.11.5066
Kosmidis S, Grammenoudi S, Papanikolopoulou K, Skoulakis EM (2010) Differential effects of Tau on the integrity and function of neurons essential for learning in Drosophila. J Neurosci 30(2):464–477. https://doi.org/10.1523/JNEUROSCI.1490-09.2010
Trushina NI, Bakota L, Mulkidjanian AY, Brandt R (2019) The evolution of tau phosphorylation and interactions. Front Aging Neurosci 11:256. https://doi.org/10.3389/fnagi.2019.00256
Mutreja Y, Combs B, Gamblin TC (2019) FTDP-17 mutations alter the aggregation and microtubule stabilization propensity of tau in an isoform-specific fashion. Biochemistry 58(6):742–754. https://doi.org/10.1021/acs.biochem.8b01039
Malia TJ, Teplyakov A, Ernst R, Wu SJ, Lacy ER, Liu X, Gilliland GL (2016) Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti, Äêtau antibody AT8. Proteins 84(4):427–434. https://doi.org/10.1002/prot.24988
Ksiezak-Reding H, Pyo HK, Feinstein B, Pasinetti GM (2003) Akt/PKB kinase phosphorylates separately Thr212 and Ser214 of tau protein in vitro. Biochim Biophys Acta - Mol Basis Dis. 1639(3):159–168. https://doi.org/10.1016/j.bbadis.2003.09.001
Ferrer I, Barrachina M, Puig B (2002) Anti-tau phospho-specific Ser 262 antibody recognizes a variety of abnormal hyper-phosphorylated tau deposits in tauopathies including Pick bodies and argyrophilic grains. Acta neuropathol 104(6). https://doi.org/10.1007/s00401-002-0600-2
De Vos A, Anandhakumar J, Van den Brande J, Verduyckt M, Franssens V, Winderickx J, Swinnen E (2011) Yeast as a model system to study tau biology. J Alzheimer’s Dis. https://doi.org/10.4061/2011/428970
Franssens V, Boelen E, Anandhakumar J, Vanhelmont T, Büttner S, Winderickx J (2010) Yeast unfolds the road map toward alpha-synuclein-induced cell death. Cell Death Differ. 17(5):746–753. https://doi.org/10.1038/cdd.2009.203
Vandebroek T, Vanhelmont T, Terwel D, Borghgraef P, Lemaire K, Snauwaert J, Winderickx J (2005) Identification and isolation of a hyperphosphorylated, conformationally changed intermediate of human protein tau expressed in yeast. Biochemistry 44(34):11466–11475. https://doi.org/10.1021/bi0506775
Liu K, Liu Y, Li L, Qin P, Iqbal J, Deng Y (1862) Qing H (2016) Glycation alter the process of Tau phosphorylation to change Tau isoforms aggregation property. Biochim Biophys Acta Mol Basis Dis 2:192–201. https://doi.org/10.1016/j.bbadis.2015.12.002
Trzeciakiewicz H, Tseng JH, Wander CM, Madden V, Tripathy A, Yuan CX, Cohen TJ (2017) A dual pathogenic mechanism links tau acetylation to sporadic tauopathy. Sci Rep 7(1):1–13. https://doi.org/10.1038/srep44102
Cohen TJ, Constance BH, Hwang AW, James M, Yuan CX (2016) Intrinsic tau acetylation is coupled to auto-proteolytic tau fragmentation. PloS one 11(7). https://doi.org/10.1371/journal.pone.0158470
Irwin DJ, Cohen TJ, Grossman M, Arnold SE, Xie SX, Lee VMY, Trojanowski JQ (2012) Acetylated tau, a novel pathological signature in Alzheimer’s disease and other tauopathies. Brain 135(3):807–818. https://doi.org/10.1093/brain/aws013
Munari F, Barracchia CG, Parolini F, Tira R, Bubacco L, Assfalg M, D’Onofrio M (2020) Semisynthetic modification of tau protein with di-ubiquitin chains for aggregation studies. Int J Mol Sci 21(12):4400. https://doi.org/10.3390/ijms21124400
Sala-Jarque J, Zimkowska K, Åvila J, Ferrer I, Del Rio JA (2022) Towards a mechanistic model of tau-mediated pathology in tauopathies: what can we learn from cell-based in vitro assays? Int J Mol Sci 23(19):11527. https://doi.org/10.3390/ijms231911527
Glasauer SM, Goderie SK, Rauch JN et al (2022) Human tau mutations in cerebral organoids induce a progressive dyshomeostasis of cholesterol. Stem Cell Rep 17(9):2127–2140. https://doi.org/10.1016/j.stemcr.2022.07.011
Shimada H, Sato Y, Sasaki T, Shimozawa A et al (2022) A next-generation iPSC-derived forebrain organoid model of tauopathy with tau fibrils by AAV-mediated gene transfer. Cell Rep Methods 2(9):100289. https://doi.org/10.1016/j.crmeth.2022.100289
Noor A, Zafar S, Zerr I (2021) Neurodegenerative proteinopathies in the proteoform spectrum-tools and challenges. Int J Mol Sci 22(3):1085. https://doi.org/10.3390/ijms22031085
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Waheed, Z., Choudhary, J., Jatala, F.H. et al. The Role of Tau Proteoforms in Health and Disease. Mol Neurobiol 60, 5155–5166 (2023). https://doi.org/10.1007/s12035-023-03387-8
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DOI: https://doi.org/10.1007/s12035-023-03387-8