TDP-43

TDP-43 est proteinum ad ADN et ARN cum elemento trans-activatione responso (communiter TAR DNA^[1] dictum) ligans. Est simul pars metabolismi ARN.

Cave: notitiae huius paginae nec praescriptiones nec consilia medica sunt.

TDP-43 TARDBP
Alia nomina	TDP43 TAR DNA-binding protein
Locus geni (homo)

Chromosoma	1 (humanum)
Locus	1p36.22 (homo)
Structura

Cognitores
OMIM	605078

Momentum in degeneratione lobulari frontotemporali, sclerosi laterali amyotrophica et morbo Alzheimeriano habere videtur, quo copiae phosphoro oneratae (hyperphosphorylatae) ubiquitinoque (ubiquitinatae) eorum proteinorum corpuscula inclusionis aggregunt.

Abbreviatura "TDP" de verbis Anglicis trans-activation response element DNA-binding protein ac numerus nominis "43" de proteini pondere, 43 kDa enim, derivantur. Nomen geni eius est TARDBP, apud homines in chromosomate 1 locatum.

Natura TDP-43

TDP-43 primum anno 1995 ab virologicis descriptum est^[2].

Structura proteini

Numerus aminoacidorum est 414, pondus suum 43 kDa est. Dominia quattuor sunt: Dominium termini N (aminoacidorum 1 - 76, abbreviatura Anglica: NTD)^[3], duo motiva recognitionis ARN aminoacidorum (106 - 176 velut 191 - 259), et dominium termini C (274 - 414). Saepe mutationes eorum geneticae cum sclerosi laterali amyotrophica consocati sunt^[4].

Neuropathologia

Saepe in morbis neurodegenerativis copiae phosphoro oneratae (hyperphosphorylatae) ubiquitinoque (ubiquitinatae)^[5] eorum proteinorum corpuscula inclusionis aggregunt^[6]. Nominantur commutationes iuxta moleculas TDP-43 proteinopathia TDP-43^[7], aggregationes amyloidi formationem. Adhuc tamen contextus incertus ob dependentiam aliarum rerum pathologicarum videtur^[8].

Videtur, ut uterque hippocampus sclerose (sclerosis hippocampalis) affectus sit^[9].

Contextus cum morbis neurodegenerativis

In quibusdam morbis neurodegenerativis degenerationum lobularium frontotemporalium et sclerosis lateralis amyotrophicae copiae proteinorum TDP-43 corpuscula inclusionis aggregunt. Nuper encephalopathia limbica, morbo Alzheimeriano similis, cum corpusculis TDP-43 inclusionis descripta est. In his corpusculis pathologicis proteina TDP-43 coniunctiones cum phosphato et ubiquitino, demum sectiones patiuntur, et insolubiles fiunt.

Adhuc non minus quam 38 mutationes geneticae apud aegrotos cum sclerosi laterali amyotrophica atque degeneratione lobulari frontotemporali in periodicis scientificis divulgatae sunt.

Degeneratio lobularis frontotemporalis

Conferatur pagina principalis Degeneratio lobularis frontotemporalis.

Sclerosis lateralis amyotrophica

Conferatur pagina principalis Sclerosis lateralis amyotrophica.

Morbus Alzheimerianus

Conferatur pagina principalis Morbus Alzheimerianus.

Relatio cum morbo Alzheimeriano iam suspicabatur^[10], insuper varia exempla molecularia accumulationis TDP-43 ope anticorporum observata sunt^[11].

Encephalopathia TDP-43 limbica

Anno 2019 genus encephalopathiae limbicae novae descriptum est, ab Nelson et al. notione encephalopathiae TDP-43 aetati relata limbicae praedominantis propositum^[12].

Notae

↑ Anglice: TAR = trans-activation response element or transactive response, DNA = deoxyribonucleic acid.
↑ Ou S. H., Wu F., et al. (Iun 1995). "Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs". Journal of virology 69 (6): 3584-96
↑ Wang A., Conicella A. E., Schmidt H. B., et al. (Mar 2018). "A single N-terminal phosphomimic disrupts TDP-43 polymerization, phase separation, and RNA splicing". The EMBO journal 37 (5): e97452 doi:10.15252/embj.201797452
↑ Conicella A. E., Zerze G. H., Mittal J., Fawzi N. L. (Sep 2016). "ALS Mutations Disrupt Phase Separation Mediated by α-Helical Structure in the TDP-43 Low-Complexity C-Terminal Domain". Structure 24 (9): 1537-49 doi:10.1016/j.str.2016.07.007
↑ Neumann M., Sampathu D. M., et al. (Oct 2006). "Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis". Science 314 (5796): 130-3
↑ Prasad A., Bharathi V., Sivalingam V., Girdhar A., Patel B. K. (Feb 2019). "Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis". Frontiers in molecular neuroscience 12: 25
↑ Forman M. S., Trojanowski J. Q., Lee V. M.-Y. (Oct 2007). "TDP-43: a novel neurodegenerative proteinopathy". Current opinion in neurobiology 17 (5): 548-55
↑ Takeda T. (Feb 2018). "Possible concurrence of TDP-43, tau and other proteins in amyotrophic lateral sclerosis/frontotemporal lobar degeneration". Neuropathology 38 (1): 72-81
↑ Nelson P. T., Schmitt F. A., et al. (Mai 2011). "Hippocampal sclerosis in advanced age: clinical and pathological features". Brain 134 (Pt 5): 1506-18
↑ Tremblay C., St-Amour I., Schneider J., Bennett D. A., Calon F. (2011). "Accumulation of transactive response DNA binding protein 43 in mild cognitive impairment and Alzheimer disease". Journal of neuropathology and experimental neurology 9 (9): 788-98
↑ Tomé S. O., Vandenberghe R., et al. (Apr 2020). "Distinct molecular patterns of TDP-43 pathology in Alzheimer's disease: relationship with clinical phenotypes". Acta neuropathologica communications 8 (1): 61
↑ Nelson P. T., Dickson D. W., Trojanowski J. Q., Jack C. R., Boyle P. A., Arfanakis K., Rademakers R., et al. (2019). "Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report". Brain 142 (6): 1503-27 , in periodicis Anglice LATE dictum

Nexus interni

Nexus externus

Hans F. (2014). Dissertatio inauguralis de TDP-43. (Anglice)

[1] Anglice: TAR = trans-activation response element or transactive response, DNA = deoxyribonucleic acid.

[2] Ou S. H., Wu F., et al. (Iun 1995). "Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs". Journal of virology 69 (6): 3584-96

[3] Wang A., Conicella A. E., Schmidt H. B., et al. (Mar 2018). "A single N-terminal phosphomimic disrupts TDP-43 polymerization, phase separation, and RNA splicing". The EMBO journal 37 (5): e97452 doi:10.15252/embj.201797452

[4] Conicella A. E., Zerze G. H., Mittal J., Fawzi N. L. (Sep 2016). "ALS Mutations Disrupt Phase Separation Mediated by α-Helical Structure in the TDP-43 Low-Complexity C-Terminal Domain". Structure 24 (9): 1537-49 doi:10.1016/j.str.2016.07.007

[5] Neumann M., Sampathu D. M., et al. (Oct 2006). "Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis". Science 314 (5796): 130-3

[6] Prasad A., Bharathi V., Sivalingam V., Girdhar A., Patel B. K. (Feb 2019). "Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis". Frontiers in molecular neuroscience 12: 25

[7] Forman M. S., Trojanowski J. Q., Lee V. M.-Y. (Oct 2007). "TDP-43: a novel neurodegenerative proteinopathy". Current opinion in neurobiology 17 (5): 548-55

[8] Takeda T. (Feb 2018). "Possible concurrence of TDP-43, tau and other proteins in amyotrophic lateral sclerosis/frontotemporal lobar degeneration". Neuropathology 38 (1): 72-81

[9] Nelson P. T., Schmitt F. A., et al. (Mai 2011). "Hippocampal sclerosis in advanced age: clinical and pathological features". Brain 134 (Pt 5): 1506-18

[10] Tremblay C., St-Amour I., Schneider J., Bennett D. A., Calon F. (2011). "Accumulation of transactive response DNA binding protein 43 in mild cognitive impairment and Alzheimer disease". Journal of neuropathology and experimental neurology 9 (9): 788-98

[11] Tomé S. O., Vandenberghe R., et al. (Apr 2020). "Distinct molecular patterns of TDP-43 pathology in Alzheimer's disease: relationship with clinical phenotypes". Acta neuropathologica communications 8 (1): 61

[12] Nelson P. T., Dickson D. W., Trojanowski J. Q., Jack C. R., Boyle P. A., Arfanakis K., Rademakers R., et al. (2019). "Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report". Brain 142 (6): 1503-27 , in periodicis Anglice LATE dictum

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