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TDP-43
TARDBP
Alia nomina TDP43
TAR DNA-binding protein
Locus geni (homo)
Chromosomate 1 locatum
Chromosoma 1 (humanum)
Locus 1p36.22 (homo)
Structura
TDP-43
Cognitores
OMIM 605078

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

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-43Recensere

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

Structura proteiniRecensere

Numerus aminoacidorum est 414, pondus suum 43 kDa est.

NeuropathologiaRecensere

Saepe in morbis neurodegenerativis copiae phosphoro oneratae (hyperphosphorylatae) ubiquitinoque (ubiquitinatae)[3] eorum proteinorum corpuscula inclusionis aggregunt[4]. Nominantur commutationes iuxta moleculas TDP-43 proteinopathia TDP-43[5], aggregationes amyloidi formationem. Adhuc tamen contextus incertus ob dependentiam aliarum rerum pathologicarum videtur[6].

Videtur, ut uterque hippocampus sclerose (sclerosis hippocampalis) affectus sit[7].

Contextus cum morbis neurodegenerativisRecensere

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 frontotemporalisRecensere

  Commentatio principalis: Degeneratio lobularis frontotemporalis

Sclerosis lateralis amyotrophicaRecensere

  Commentatio principalis: Sclerosis lateralis amyotrophica

Morbus AlzheimerianusRecensere

  Commentatio principalis: Morbus Alzheimerianus

Relatio cum morbo Alzheimeriano iam suspicabatur[8], insuper varia exempla molecularia accumulationis TDP-43 ope anticorporum observata sunt[9].

Encephalopathia TDP-43 limbicaRecensere

Anno 2019 genus encephalopathiae limbicae novae descriptum est, ab Nelson et al. notione encephalopathiae TDP-43 aetati relata limbicae praedominantis propositum[10].

NotaeRecensere

  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. 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 
  4. 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 
  5. 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 
  6. 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 
  7. 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 
  8. 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 
  9. 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 
  10. 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 externusRecensere

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