Aggregation-prone TDP-43 sequesters and drives pathological transitions of free nuclear TDP-43

Ling SC, Polymenidou M, Cleveland DW (2013) Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 79(3):416–438

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133

Article  CAS  PubMed  Google Scholar 

Polymenidou M, Lagier-Tourenne C, Hutt KR, Huelga SC, Moran J, Liang TY et al (2011) Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat Neurosci 14(4):459–468

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M et al (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 14(4):452–458

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ayala YM, De Conti L, Avendaño-Vázquez SE, Dhir A, Romano M, D’Ambrogio A et al (2011) TDP-43 regulates its mRNA levels through a negative feedback loop. Embo J 30(2):277–288

Article  CAS  PubMed  Google Scholar 

Buratti E, Baralle FE (2010) The multiple roles of TDP-43 in pre-mRNA processing and gene expression regulation. RNA Biol 7(4):420–429

Article  CAS  PubMed  Google Scholar 

Keating SS, San Gil R, Swanson MEV, Scotter EL, Walker AK (2022) TDP-43 pathology: from noxious assembly to therapeutic removal. Progr Neurobiol 211:102229

Article  CAS  Google Scholar 

Barmada SJ, Skibinski G, Korb E, Rao EJ, Wu JY, Finkbeiner S (2010) Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis. J Neurosci 30(2):639–649

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dyer MS, Reale LA, Lewis KE, Walker AK, Dickson TC, Woodhouse A et al (2021) Mislocalisation of TDP-43 to the cytoplasm causes cortical hyperexcitability and reduced excitatory neurotransmission in the motor cortex. J Neurochem 157(4):1300–1315

Article  CAS  PubMed  Google Scholar 

Vatsavayai SC, Yoon SJ, Gardner RC, Gendron TF, Vargas JNS, Trujillo A et al (2016) Timing and significance of pathological features in C9orf72 expansion-associated frontotemporal dementia. Brain 139(12):3202–3216

Article  PubMed  PubMed Central  Google Scholar 

Nana AL, Sidhu M, Gaus SE, Hwang J-HL, Li L, Park Y et al (2019) Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology. Acta Neuropathol 137(1):27–46

Article  PubMed  Google Scholar 

Braak H, Del Tredici K (2018) Anterior cingulate cortex TDP-43 pathology in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 77(1):74–83

Article  PubMed  Google Scholar 

Igaz LM, Kwong LK, Lee EB, Chen-Plotkin A, Swanson E, Unger T et al (2011) Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J Clin Investig 121(2):726–738

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu EY, Russ J, Cali CP, Phan JM, Amlie-Wolf A, Lee EB (2019) Loss of nuclear TDP-43 Is associated with decondensation of LINE retrotransposons. Cell Rep 27(5):1409-1421.e6

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu LS, Cheng WC, Chen CY, Wu MC, Wang YC, Tseng YH et al (2019) Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons. Acta Neuropathol Commun 7(1):50

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jeong YH, Ling JP, Lin SZ, Donde AN, Braunstein KE, Majounie E et al (2017) Tdp-43 cryptic exons are highly variable between cell types. Mol Neurodegener 12(1):13

Article  PubMed  PubMed Central  Google Scholar 

Walker AK, Spiller KJ, Ge G, Zheng A, Xu Y, Zhou M et al (2015) Functional recovery in new mouse models of ALS/FTLD after clearance of pathological cytoplasmic TDP-43. Acta Neuropathol 130(5):643–660

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eck RJ, Kraemer BC, Liachko NF (2021) Regulation of TDP-43 phosphorylation in aging and disease. Geroscience 43(4):1605–1614

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neumann M, Kwong LK, Lee EB, Kremmer E, Flatley A, Xu Y et al (2009) Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies. Acta Neuropathol 117(2):137–149

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y et al (2008) Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol 64(1):60–70

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cohen TJ, Hwang AW, Restrepo CR, Yuan CX, Trojanowski JQ, Lee VM (2015) An acetylation switch controls TDP-43 function and aggregation propensity. Nat Commun 6:5845

Article  CAS  PubMed  Google Scholar 

Wang P, Wander CM, Yuan C-X, Bereman MS, Cohen TJ (2017) Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program. Nat Commun 8(1):82

Article  PubMed  PubMed Central  Google Scholar 

Kametani F, Obi T, Shishido T, Akatsu H, Murayama S, Saito Y et al (2016) Mass spectrometric analysis of accumulated TDP-43 in amyotrophic lateral sclerosis brains. Sci Rep 6:23281

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen Y, Cohen TJ (2019) Aggregation of the nucleic acid–binding protein TDP-43 occurs via distinct routes that are coordinated with stress granule formation. J Biol Chem 294(10):3696–3706

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu H, Lu S, Gasior K, Singh D, Vazquez-Sanchez S, Tapia O et al (2021) HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science 371(6529):eabb4309

Article  CAS  PubMed  Google Scholar 

Zacco E, Martin SR, Thorogate R, Pastore A (2018) The RNA-recognition motifs of TAR DNA-binding protein 43 may play a role in the aberrant self-assembly of the protein. Front Mol Neurosci 11:372

Article  CAS  PubMed  PubMed Central  Google Scholar 

Flores BN, Li X, Malik AM, Martinez J, Beg AA, Barmada SJ (2019) An intramolecular salt bridge linking TDP43 RNA binding, protein stability, and TDP43-dependent neurodegeneration. Cell Rep 27(4):1133-1150.e8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pérez-Berlanga M, Wiersma VI, Zbinden A, De Vos L, Wagner U, Foglieni C et al (2022) TDP-43 oligomerization and RNA binding are codependent but their loss elicits distinct pathologies. bioRxiv: 2022.05.23.493029

Chen HJ, Topp SD, Hui HS, Zacco E, Katarya M, McLoughlin C et al (2019) RRM adjacent TARDBP mutations disrupt RNA binding and enhance TDP-43 proteinopathy. Brain 142(12):3753–3770

Article  PubMed  PubMed Central  Google Scholar 

Hallegger M, Chakrabarti AM, Lee FCY, Lee BL, Amalietti AG, Odeh HM et al (2021) TDP-43 condensation properties specify its RNA-binding and regulatory repertoire. Cell 184(18):4680-4696

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maharana S, Wang J, Papadopoulos DK, Richter D, Pozniakovsky A, Poser I et al (2018) RNA buffers the phase separation behavior of prion-like RNA binding proteins. Science 360(6391):918-921

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mann JR, Gleixner AM, Mauna JC, Gomes E, DeChellis-Marks MR, Needham PG et al (2019) RNA binding antagonizes neurotoxic phase transitions of TDP-43. Neuron 102(2):321-338.e8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gasset-Rosa F, Lu S, Yu H, Chen C, Ze M, Guo L et al (2019) Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death. Neuron 102(2):339-357.e7

Article  CAS  PubMed  PubMed Central  Google Scholar 

McGurk L, Gomes E, Guo L, Mojsilovic-Petrovic J, Tran V, Kalb RG et al (2018) Poly(ADP-Ribose) prevents pathological phase separation of TDP-43 by promoting liquid demixing and stress granule localization. Mol Cell 71(5):703–717

Article  CAS  PubMed  PubMed Central  Google Scholar 

Molliex A, Temirov J, Lee J, Coughlin M,

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