Beta-secretasis 1

Beta-secretasis 1
Alia nomina	BACE1, ASP2, BACE, HSPC104
Numerus EC	3.4.23.46 aspartylproteasis
Locus geni (homo)

Chromosoma	11 (humanum)
Locus	11q23.3 (homo)

Substratum	proteinum praecursor amyloidi (APP)
Fontes externae	OMIM: 604252

Beta-secretasis 1 (Numerus EC: 3.4.23.46 - aspartylproteasum) sive memapsinum-2 est unum e duobus enzymis generationis amyloidi beta. Munus vero partialis in organismo regeneratio nervorum laesorum putatur. In morbo Alzheimeriano ea ß-amyloida in cerebro aggregunt^[1], maculas seniles ("senile plaques") formantes.

Hodie inhibitores beta-secretasis 1 sunt aspirantes medicamentorum contra morbum Alzheimerianum^[2].

In Suecia beta-secretasis-2, alia beta-secretasis, investigata est.

Natura beta-secetasis 1

Genetica

Nomen geni ß-secretasis 1 est BACE1 locus cuius geneticus in chromosomate 11 humano invenitur (11q23.3). Numerus aminoacidorum 501 est.

Natura physiologia

Effectus beta-secretasis formationis amyloidi beta. Infra membranam spatium intracellulare, supra foris. Beta-secretasis extra cellulem de APP fragmentum dissecat. Dehinc gamma-secretasis intra membranam cellulare altrum fragmentum, amyloid enim beta, dissecat.

Formatio amyloidi beta per duos gradus oritur: Primo beta-secretasis 1 amyloidum praecursor proteinum (APP), typo 1 proteinorum membranaceorum attributum, dissecat. Postea gamma-secretasis amyloidum beta format.
APP est proteinum transmembranaceum: pars proteini est intra cellulam, pars intra membranam, pars extra cellularem. Introrsum C-terminus locatum, extrorsum N-terminus. Loco sectionis beta-secretasis extra cellulam duo fragmenta generat^[3]: C99 (membranae affixum, unde pars transmembranacea) et sAPPß (liberum, extra cellulam).

Contextus in organismo

Momentum corporis iam incertum restat, at distributio enzymi intra nervos laesos conspicue est, inde munus regenerationis illorum nervorum putatur^[4].

Historia

Anno 1999 plures greges scientifici clonizatione enzymum proteasem conspexerunt^[5]^[6]^[7], tum saepe ASP 2 dictum. Quia enzymum (cum beta-secretasis 2) amyloidum beta ex amyloidum praecursor proteinum cernit, enzymum hoc nomen BACE-1 (beta [situs] amyloidum [praecursor proteinum] cernens enzymum) vocatur. Paulo post non solum enzymum cum 501 aminoacidorum ("BACE1-501"), sed etiam cum deletionibus: BACE1-476 (minus 25 aminoacidorum), BACE1-457 (-44) atque BACE1-32 (-69)^[8].

Iam ante annum 2002 disputationes usus inhibitorum beta-secretasis 1 in morbo Alzheimeriano tractando emergebant^[9]. Anno 2005 effectus inhibitionis in rattis divulgatus est^[10]. Tamen applicatio medicamentorum novorum (post inhibitores cholinesterasis ut Donepezili, Rivastigmini) in hominibus eventus adhuc parum validi eliciebant, ut exemplum Tramiprosati ostendavit^[11].

Notae

↑ Walsh D. M., Teplow D. B. (2012). "Alzheimer's disease and the amyloid β-protein". Progress in molecular biology and translational science 107: 101-24 .
↑ Yan R., Vassar R. (2014). "Targeting the β secretase BACE1 for Alzheimer's disease therapy". The Lancet. Neurology. 13 (3): 319-29 .
↑ Vassar R., Kovacs D. M., Yan R., Wong P. C. (2009). "The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential". The journal of neuroscience 29 (41): 12787-94
↑ Hu X., Hu J., Dai L., Trapp B., Yan R. (2015). "Axonal and Schwann cell BACE1 is equally required for remyelination of peripheral nerves". The journal of neuroscience 35 (9): 3806-14
↑ Yan R1, Bienkowski M. J., Shuck M. E., Miao H., Tory M. C., Pauley A. M., Brashier J. R., Stratman N. C., Mathews W. R., Buhl A. E, et al. (1999). "Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity". Nature 402 (6761): 533-7
↑ Hussain I., Powell D., Howlett D. R., Tew D. G., Meek T. D., Chapman C., Gloger I. S., Murphy K. E., Southan C. D., Ryan D. M., , et al. (1999). "Identification of a novel aspartic protease (Asp 2) as beta-secretase". Molecular and cellular neuroscience 14 (6): 419-27
↑ Sinha S., Anderson J. P., Barbour R., Basi G. S., Caccavello R., Davis D., Doan M., Dovey H. F., Frigon N., Hong J., Jacobson-Croak K., et al. (1999). "Purification and cloning of amyloid precursor protein beta-secretase from human brain". Nature 402 (6761): 537-40
↑ Tanahashi H., Tabira T. (2001). "Three novel alternatively spliced isoforms of the human beta-site amyloid precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-peptide production". Neuroscience letters 307 (1): 9-12
↑ Maiorini A. F., Gaunt M. J., Jacobsen T. M., McKay A. E., Waldman L. D., Raffa R. B. (2002). "Potential novel targets for Alzheimer pharmacotherapy: I. Secretases". Journal of clinical pharmacy and therapa 27 (3): 169-83
↑ Singer O., Marr R. A., Rockenstein E., Crews L., Coufal N. G., Gage F. H., Verma I. M., Masliah E. (2005). "Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model". Nature neuroscience 8 (10): 1343-9
↑ Caltagirone C., Ferrannini L., Marchionni N., Nappi G., Scapagnini G., Trabucchi M. (2012). "The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review". Aging clinical and experimental research 24 (6): 580-7

Nexus interni

[1] Walsh D. M., Teplow D. B. (2012). "Alzheimer's disease and the amyloid β-protein". Progress in molecular biology and translational science 107: 101-24 .

[2] Yan R., Vassar R. (2014). "Targeting the β secretase BACE1 for Alzheimer's disease therapy". The Lancet. Neurology. 13 (3): 319-29 .

[3] Vassar R., Kovacs D. M., Yan R., Wong P. C. (2009). "The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential". The journal of neuroscience 29 (41): 12787-94

[4] Hu X., Hu J., Dai L., Trapp B., Yan R. (2015). "Axonal and Schwann cell BACE1 is equally required for remyelination of peripheral nerves". The journal of neuroscience 35 (9): 3806-14

[5] Yan R1, Bienkowski M. J., Shuck M. E., Miao H., Tory M. C., Pauley A. M., Brashier J. R., Stratman N. C., Mathews W. R., Buhl A. E, et al. (1999). "Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity". Nature 402 (6761): 533-7

[6] Hussain I., Powell D., Howlett D. R., Tew D. G., Meek T. D., Chapman C., Gloger I. S., Murphy K. E., Southan C. D., Ryan D. M., , et al. (1999). "Identification of a novel aspartic protease (Asp 2) as beta-secretase". Molecular and cellular neuroscience 14 (6): 419-27

[7] Sinha S., Anderson J. P., Barbour R., Basi G. S., Caccavello R., Davis D., Doan M., Dovey H. F., Frigon N., Hong J., Jacobson-Croak K., et al. (1999). "Purification and cloning of amyloid precursor protein beta-secretase from human brain". Nature 402 (6761): 537-40

[8] Tanahashi H., Tabira T. (2001). "Three novel alternatively spliced isoforms of the human beta-site amyloid precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-peptide production". Neuroscience letters 307 (1): 9-12

[9] Maiorini A. F., Gaunt M. J., Jacobsen T. M., McKay A. E., Waldman L. D., Raffa R. B. (2002). "Potential novel targets for Alzheimer pharmacotherapy: I. Secretases". Journal of clinical pharmacy and therapa 27 (3): 169-83

[10] Singer O., Marr R. A., Rockenstein E., Crews L., Coufal N. G., Gage F. H., Verma I. M., Masliah E. (2005). "Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model". Nature neuroscience 8 (10): 1343-9

[11] Caltagirone C., Ferrannini L., Marchionni N., Nappi G., Scapagnini G., Trabucchi M. (2012). "The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review". Aging clinical and experimental research 24 (6): 580-7

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