Alpha-synucleinum

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Synucleinum alpha
Alia nomina SNCA, NACP, PARK1, PARK4, PD1
Synucleinum alpha
Fontes externae OMIM: 163890
Locus geni (homo)
Chromosomate 4 locatum
Chromosoma 4 (humanum)

Alpha-synucleinum (sive, raro, NACP) est unum ex tribus proteinis familiae synucleinorum ex 140 aminoacidis compositum. Ut omnia synucleina alpha-synucleinum adhuc solum in vertebratis inventum est, tunc in cerebrorum synapsibus praesynapticis[1]. Adhuc quaedam functio certo nota non est. Anticorpus contra alpha-synucleinum in morbo Parkinson tractando investigatur.

Sicubi in cerebro accidat, ut laesiones cerebrales alpha-synucleinis glomeratis sibi forment, ut in variis morbis neurodegenerativis, ii gregi synucleopathiarum supponuntur[2].

Nomen geni sui dicitur SCNA. Mutationes geni geneticae cum morbo Parkinson sociatae sunt.

Morbi cum alpha-synucleini accumulatione coniuncti vocitantur synucleinopathiae.

Natura synucleini[recensere | fontem recensere]

Structura[recensere | fontem recensere]

Alpha-synucleinum ex centum quadraginta aminoacidis formatur[3]. Nomen priscum NACP erat, et fragmentum eius, NAC, in amyloidis morbo Alzheimeriano aegrotorum adcognitum est.

Synucleina[recensere | fontem recensere]

Synucleina sunt proteina parva, solubilia et praecipue in tela nervosa et certis tumoribus inventa. In organismo humano tres familiae descripta sunt: alpha, beta, gamma[4]. Alpha-synucleina nexus cum morbo Parkinson et aliis morbis neurodegenerativis ostendunt. Beta-synucleina autem quasi alpha-synucleinis antagonistae videbatur. Gamma-synucleinum in certis tumoribus, in oculorum morbis inventum est. Adhuc synucleina in vertebratis descripta sunt[5].

Genetica alpha-synucleini[recensere | fontem recensere]

Genum alpha-synucleini SCNA vocatur et humano in chromosomate 4 locatum est (4q22.1)[6]. Geno SNCA longitudinis 146[7] kilobasium (kb) sex exona sunt ex quibus quinque proteino scribunt[8].

Significatio pathologica[recensere | fontem recensere]

Morborum neurodegenerativorum cum corpusculis Leweyi, ut morbus Parkinson vel dementia cum corpusculis Leweyi, cursus vagior ostendit. Multitudo autem alpha-synucleini aggregati, per haec amyloidum formans, in cerebro et dementiae initium velut cursus morbi indicat[9]. Putatur, ut diversitates alpha-synucleini cursus synucleinopathiae diversos explicare possint[10]. Nuper aggregationem pathologicam in drosophila melanogastro per monomerum AS69 inhiberi posse demonstratum est[11].

Anticorpus contra alpha-synucleinum[recensere | fontem recensere]

Conatus et experimentum est therapia morbi Parkinson cum anticorporibus contra alpha-synucleinum[12]. Effectus anticorpus monoclonalis PRX002 (Prasinezumabum)/RG7935 nunc investigatur[13].

Notae[recensere | fontem recensere]

  1. ↑ Jakes R, Spillantini MG, Goedert M (1994). "Identification of two distinct synucleins from human brain". FEBS Lett 345 (1): 27-32 
  2. ↑ Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, Ischiropoulos H, Trojanowski JQ, Lee VM (2000). "Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions". Science 290 (5493): 985-9 
  3. ↑ Uéda K., Fukushima H., et al. (Dec 1993). "Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease". Proceedings of the National Academy of Sciences of the United States of America 90 (23): 11282-6 
  4. ↑ Surguchov A (2008). "Molecular and cellular biology of synucleins". Int Rev Cell Mol Biol 270: 225-317 
  5. ↑ Surguchov A (2015). "Intracellular Dynamics of Synucleins: "Here, There and Everywhere"". Int Rev Cell Mol Biol 320: 103-69 
  6. ↑ Chen X., de Silva H. A., Pettenati M. J., Rao P. N., St George-Hyslop P., Roses A. D., Xia Y., Horsburgh K., Ueda K., Saitoh T. (1995). "The human NACP/alpha-synuclein gene: chromosome assignment to 4q21.3-q22 and TaqI RFLP Analysis". Genomics 26: 425-7 
  7. ↑ mus: 118 kb
  8. ↑ Touchman J. W., Dehejia A., Chiba-Falek O., Cabin D. E., Schwartz J. R., Orrison B. M., Polymeropoulos M. H., Nussbaum R. L. (2001). "Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element". Genome research 11 (1): 78-86 
  9. ↑ Irwin DJ, Grossman M, Weintraub D, Hurtig HI, Duda JE, Xie SX, Lee EB, Van Deerlin VM, Lopez OL, Kofler JK, Nelson PT, Jicha GA, Woltjer R, Quinn JF, Kaye J, Leverenz JB, Tsuang D, Longfellow K, Yearout D, Kukull W, Keene CD, Montine TJ, Zabetian CP, Trojanowski JQ (2017). "Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis". Lancet Neurol 16(1): 55-65 
  10. ↑ Holec S. A. M., Woerman A. L. (Mai 2020). "Evidence of Distinct α-Synuclein Strains Underlying Disease Heterogeneity". Acta neuropathologica 
  11. ↑ Agerschou E. D., Flagmeier P., Saridaki T., Galvagnion C., Komnig D., Heid L., Prasad V., Shaykhalishahi H., et al. (Aug 2019). "An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils". Elife (8): e46112 
  12. ↑ Jankovic J., Goodman I., Safirstein B., Marmon T. K., Schenk D. B., Koller M., Zago W., Ness D. K., Griffith S. G., Grundman M., Soto J., Ostrowitzki S., Boess F. G., Martin-Facklam M., Quinn J. F., Isaacson S. H., Omidvar O., Ellenbogen A., Kinney G. G. (2018). "Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial". JAMA Neurol: doi: 10.1001/jamaneurol.2018.1487 
  13. ↑ Cuius investigatio PASADENA nominata est.

Nexus interni

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