Reappraisal of the anatomical spreading and propagation hypothesis about TDP-43 aggregation in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
ALS
FTLD
TDP-43
neural projections
propagation
Journal
Neuropathology : official journal of the Japanese Society of Neuropathology
ISSN: 1440-1789
Titre abrégé: Neuropathology
Pays: Australia
ID NLM: 9606526
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
01
11
2019
revised:
24
12
2019
accepted:
26
12
2019
pubmed:
12
3
2020
medline:
15
10
2021
entrez:
12
3
2020
Statut:
ppublish
Résumé
Neuronal inclusion of transactivation response DNA-binding protein 43 kDa (TDP-43) is known to be a pathologic hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TDP-43, which is physiologically a nuclear protein, is mislocalized from the nucleus and aggregated within the cytoplasm of affected neurons in ALS and FTLD patients. Neuropathologic or experimental studies have addressed mechanisms underlying spreading of TDP-43 inclusions in the central nervous system of ALS and FTLD patients. On the basis of postmortem observations, it is hypothesized that TDP-43 inclusions spread along the neural projections. A centrifugal gradient of TDP-43 pathology in certain anatomical systems and axonal or synaptic aggregation of TDP-43 may support the hypothesis. Experimental studies have revealed cell-to-cell propagation of aggregated or truncated TDP-43, which indicates a direct transmission of TDP-43 inclusions to contiguous cells. However, discrepancies remain between the cell-to-cell propagation suggested in the experimental models and the anatomical spreading of TDP-43 aggregations based on postmortem observations. Trans-synaptic transmission, rather than the direct cell-to-cell transmission, may be consistent with the anatomical spreading of TDP-43 aggregations, but cellular mechanisms of trans-synaptic transmission of aggregated proteins remain to be elucidated. Moreover, the spreading of TDP-43 inclusions varies among patients and genetic backgrounds, which indicates host-dependent factors for spreading of TDP-43 aggregations. Perturbation of cellular TDP-43 clearance may be a possible factor modifying the aggregation and spreading. This review discusses postmortem and experimental evidence that address mechanisms of spreading of TDP-43 pathology in the central nervous system of ALS and FTLD patients.
Substances chimiques
DNA-Binding Proteins
0
TARDBP protein, human
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
426-435Informations de copyright
© 2020 Japanese Society of Neuropathology.
Références
Buratti E, Dörk T, Zuccato E, Pagani F, Romano M, Baralle FE. Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J 2001; 20: 1774-1784.
Neumann M, Sampathu DM, Kwong LK et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314: 130-133.
Arai T, Hasegawa M, Akiyama H et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2006; 351: 602-611.
Braak H, Brettschneider J, Ludolph AC, Lee VM, Trojanowski JQ, Del Tredici K. Amyotrophic lateral sclerosis-a model of corticofugal axonal spread. Nat Rev Neurol 2013; 9: 708-714.
Brettschneider J, Del Tredici K, Irwin DJ et al. Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta Neuropathol 2014; 127: 423-439.
Brettschneider J, Del Tredici K, Toledo JB et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 2013; 74: 20-38.
Neary D, Snowden JS, Gustafson L et al. Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology 1998; 51: 1546-1554.
Halliday G, Bigio EH, Cairns NJ, Neumann M, Mackenzie IR, Mann DM. Mechanisms of disease in frontotemporal lobar degeneration: Gain of function versus loss of function effects. Acta Neuropathol 2012; 124: 373-382.
Josephs KA, Hodges JR, Snowden JS et al. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol 2011; 122: 137-153.
Mann DMA, Snowden JS. Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype. Brain Pathol 2017; 27: 723-736.
Cairns NJ, Neumann M, Bigio EH et al. TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 2007; 171: 227-240.
Sampathu DM, Neumann M, Kwong LK et al. Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. Am J Pathol 2006; 169: 1343-1352.
Mackenzie IR, Neumann M, Baborie A et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 2011; 122: 111-113.
Hasegawa M, Arai T, Nonaka T et al. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol 2008; 64: 60-70.
Igaz LM, Kwong LK, Lee EB et al. Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J Clin Invest 2011; 121: 726-738.
Nonaka T, Masuda-Suzukake M, Arai T et al. Prion-like properties of pathological TDP-43 aggregates from diseased brains. Cell Rep 2013; 4: 124-134.
Winton MJ, Igaz LM, Wong MM, Kwong LK, Trojanowski JQ, Lee VM. Disturbance of nuclear and cytoplasmic TAR DNA-binding protein (TDP-43) induces disease-like redistribution, sequestration, and aggregate formation. J Biol Chem 2008; 283: 13302-13309.
Geser F, Martinez-Lage M, Robinson J et al. Clinical and pathological continuum of multisystem TDP-43 proteinopathies. Arch Neurol 2009; 66: 180-189.
Riku Y, Watanabe H, Yoshida M et al. Lower motor neuron involvement in TAR DNA-binding protein of 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis. JAMA Neurol 2014; 71: 172-179.
Josephs KA, Stroh A, Dugger B, Dickson DW. Evaluation of subcortical pathology and clinical correlations in FTLD-U subtypes. Acta Neuropathol 2009; 118: 349-358.
Zhang H, Tan CF, Mori F et al. TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia. Acta Neuropathol 2008; 115: 115-122.
Riku Y, Atsuta N, Yoshida M et al. Differential motor neuron involvement in progressive muscular atrophy: A comparative study with amyotrophic lateral sclerosis. BMJ Open 2014; 4: e005213.
Wils H, Kleinberger G, Janssens J et al. TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A 2010; 107: 3858-3863.
Baskaran P, Shaw C, Guthrie S. TDP-43 causes neurotoxicity and cytoskeletal dysfunction in primary cortical neurons. PLoS One 2018; 13: e0196528.
Ebstein SY, Yagudayeva I, Shneider NA. Mutant TDP-43 causes early-stage dose-dependent motor neuron degeneration in a TARDBP knockin mouse model of ALS. Cell Rep 2019; 26: 364-373.
Laferrière F, Maniecka Z, Pérez-Berlanga M et al. TDP-43 extracted from frontotemporal lobar degeneration subject brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates. Nat Neurosci 2019; 22: 65-77.
Lee EB, Lee VM, Trojanowski JQ. Gains or losses: Molecular mechanisms of TDP43-mediated neurodegeneration. Nat Rev Neurosci 2011; 13: 38-50.
Xu ZS. Does a loss of TDP-43 function cause neurodegeneration? Mol Neurodegener 2012; 7: 27.
Yang C, Wang H, Qiao T et al. Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2014; 111: E1121-E1129.
Mitra J, Guerrero EN, Hegde PM et al. Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects. Proc Natl Acad Sci U S A 2019 (in press); 116: 4696-4705.
Wu LS, Cheng WC, Chen CY et al. Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons. Acta Neuropathol Commun 2019; 7: 50.
Donde A, Sun M, Ling JP et al. Splicing repression is a major function of TDP-43 in motor neurons. Acta Neuropathol 2019 (in press); 138: 813-826.
LaRocca TJ, Mariani A, Watkins LR, Link CD. TDP-43 knockdown causes innate immune activation via protein kinase R in astrocytes. Neurobiol Dis 2019; 132: 104514.
Kanouchi T, Ohkubo T, Yokota T. Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation? J Neurol Neurosurg Psychiatry 2012; 83: 739-745.
Giordana MT, Piccinini M, Grifoni S et al. TDP-43 redistribution is an early event in sporadic amyotrophic lateral sclerosis. Brain Pathol 2010; 20: 351-360.
Braak H, Ludolph AC, Neumann M, Ravits J, Del Tredici K. Pathological TDP-43 changes in Betz cells differ from those in bulbar and spinal α-motoneurons in sporadic amyotrophic lateral sclerosis. Acta Neuropathol 2017; 133: 79-90.
Takeda T, Seilhean D, Le Ber I et al. Amygdala TDP-43 pathology in frontotemporal lobar degeneration and motor neuron disease. J Neuropathol Exp Neurol 2017; 76: 800-812.
Riku Y, Watanabe H, Yoshida M et al. Marked involvement of the striatal efferent system in TAR DNA-binding protein 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2016; 75: 801-811.
Takeda T, Iijima M, Uchihara T et al. TDP-43 pathology progression along the olfactory pathway as a possible substrate for olfactory impairment in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2015; 74: 547-556.
Takeda T, Uchihara T, Arai N, Mizutani T, Iwata M. Progression of hippocampal degeneration in amyotrophic lateral sclerosis with or without memory impairment: Distinction from Alzheimer disease. Acta Neuropathol 2009; 117: 35-44.
Hiji M, Takahashi T, Fukuba H, Yamashita H, Kohriyama T, Matsumoto M. White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin. Acta Neuropathol 2008; 116: 183-191.
Neumann M, Kwong LK, Truax AC et al. TDP-43-positive white matter pathology in frontotemporal lobar degeneration with ubiquitin-positive inclusions. J Neuropathol Exp Neurol 2007; 66: 177-183.
Riku Y, Watanabe H, Yoshida M et al. Pathologic involvement of glutamatergic striatal inputs from the cortices in TAR DNA-binding protein 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2017; 76: 759-768.
Fallini C, Bassell GJ, Rossoll W. The ALS disease protein TDP-43 is actively transported in motor neuron axons and regulates axon outgrowth. Hum Mol Genet 2012; 21: 3703-3718.
Iguchi Y, Eid L, Parent M et al. Exosome secretion is a key pathway for clearance of pathological TDP-43. Brain 2016; 139: 3187-3201.
Porta S, Xu Y, Restrepo CR et al. Patient-derived frontotemporal lobar degeneration brain extracts induce formation and spreading of TDP-43 pathology in vivo. Nat Commun 2018; 9: 4220.
Nishihira Y, Tan CF, Onodera O et al. Sporadic amyotrophic lateral sclerosis: Two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. Acta Neuropathol 2008; 116: 169-182.
Sreedharan J, Blair IP, Tripathi VB et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319: 1668-1672.
van Deerlin VM, Leverenz JB, Bekris LM et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: A genetic and histopathological analysis. Lancet Neurol 2008; 7: 409-416.
Yokoseki A, Shiga A, Chun-Feng T et al. TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 2008; 63: 538-542.
Okamoto K, Fujita Y, Hoshino E et al. An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation. Neuropathology 2015; 35: 462-468.
Brady OA, Meng P, Zheng Y, Mao Y, Hu F. Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1. J Neurochem 2011; 116: 248-259.
Zhang YJ, Gendron TF, Xu YF, Ko LW, Yen SH, Petrucelli L. Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR DNA binding protein-43 C-terminal fragments. Mol Neurodegener 2010; 5: 33.
Budini M, Buratti E, Morselli E, Criollo A. Autophagy and its impact on neurodegenerative diseases: New roles for TDP-43 and C9orf72. Front Mol Neurosci 2017; 10: 170.
Filimonenko M, Stuffers S, Raiborg C et al. Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J Cell Biol 2007; 179: 485-500.
Wang X, Fan H, Ying Z, Li B, Wang H, Wang G. Degradation of TDP-43 and its pathogenic form by autophagy and the ubiquitin proteasome system. Neurosci Lett 2010; 469: 112-116.
Mizuno Y, Amari M, Takatama M, Aizawa H, Mihara B, Okamoto K. Immunoreactivities of p62, an ubiqutin-binding protein, in the spinal anterior horn cells of patients with amyotrophic lateral sclerosis. J Neurol Sci 2006; 249: 13-18.
Sasaki S. Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2011; 70: 349-359.
Barmada SJ, Serio A, Arjun A et al. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol 2014; 10: 677-685.
Tashiro Y, Urushitani M, Inoue H et al. Motor neuron-specific disruption of proteasomes, but not autophagy, replicates amyotrophic lateral sclerosis. J Biol Chem 2012; 287: 42984-42994.
Fecto F, Yan J, Vemula SP et al. SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol 2011; 68: 1440-1446.
Hirano M, Nakamura Y, Saigoh K et al. Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis. Neurology 2013; 80: 458-463.
Le Ber I, Camuzat A, Guerreiro R et al. SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. JAMA Neurol 2013; 70: 1403-1410.
Teyssou E, Takeda T, Lebon V et al. Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: Genetics and neuropathology. Acta Neuropathol 2013; 125: 511-522.
Deng HX, Chen W, Hong ST et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 2011; 477: 211-215.
Gkazi SA, Troakes C, Topp S et al. Striking phenotypic variation in a family with the P506S UBQLN2 mutation including amyotrophic lateral sclerosis, spastic paraplegia, and frontotemporal dementia. Neurobiol Aging 2019; 73: 229.e5-229.e9.
Watts GD, Wymer J, Kovach MJ et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin- containing protein. Nat Genet 2004; 36: 377-381.
Cruts M, Gijselinck I, van der Zee J et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442: 920-924.
Baker M, Mackenzie IR, Pickering-Brown SM et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006; 442: 916-919.
Maruyama H, Morino H, Ito H et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature 2010; 465: 223-226.
Hardy J, Rogaeva E. Motor neuron disease and frontotemporal dementia: Sometimes related, sometimes not. Exp Neurol 2014; 262: 75-83.
Smith KR, Damiano J, Franceschetti S et al. Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet 2012; 90: 1102-1107.
Sellier C, Campanari ML, Julie Corbier C et al. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death. EMBO J 2016; 35: 1276-1297.
Shi Y, Lin S, Staats KA et al. Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons. Nat Med 2018; 24: 313-325.
Webster CP, Smith EF, Bauer CS et al. The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. EMBO J 2016; 35: 1656-1676.
Waite AJ, Bäumer D, East S et al. Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiol Aging 2014; 35: 1779.e5-1779.e13.
Riku Y, Duyckaerts C, Boluda S et al. Increased prevalence of granulovacuolar degeneration in C9orf72 mutation. Acta Neuropathol 2019; 138: 783-793.