関: amyloid precursor protein secretase、beta-secretase、gamma-secretase、secretase

WordNet

first in order of importance; "the alpha male in the group of chimpanzees"; "the alpha star in a constellation is the brightest or main star"
the 1st letter of the Greek alphabet
the beginning of a series or sequence; "the Alpha and Omega, the first and the last, the beginning and the end"--Revelations
early testing stage of a software or hardware product; "alpha version"
a set of enzymes believed to snip pieces off a longer protein producing fragments of amyloid protein that bunch up and create amyloid protein plaques in brain tissue (the pathological hallmark of Alzheimers)
any high mountain

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アルファ(ギリシア語アルファベットの第1字A,α;英語のA,aに相当) / アルファ星(星座の主星)
高山,高峰

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/26 23:10:45」(JST)

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Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer's disease-associated peptide amyloid beta when APP is instead processed by beta secretase and gamma secretase. The alpha-secretase pathway is the predominant APP processing pathway. Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway in APP processing. Alpha secretases are members of the ADAM ('a disintegrin and metalloprotease domain') family, which are expressed on the surfaces of cells and anchored in the cell membrane. Several such proteins, notably ADAM10, have been identified as possessing alpha-secretase activity. Upon cleavage by alpha secretases, APP releases its extracellular domain - a fragment known as APPsα - into the extracellular environment in a process known as ectodomain shedding.^[1]

Cleavage of APP via alpha, beta and gamma secretase; defined functions on APP are coloured

ADAM10 consists of two protein domains, a disintegrin domain and a prodomain; however, only the prodomain is required for APP processing.^[2] Other ADAM proteins, ADAM17 (also called TACE, tumor necrosis factor-α converting enzyme),^[3] ADAM9,^[4] and ADAM19^[5] have also been identified as alpha secretases; extracellular expression of mutant ADAM9 (also known as MDC9 or meltrin gamma) lacking the membrane anchor domain has been suggested as one of many possible means of Alzheimer's prevention and treatment exploiting the alpha secretase pathway.^[6] Two distinct modalities of alpha-secretase activity have been observed in cells; constitutive activity occurs mainly at the cell surface ^[7] and is independent of regulatory mechanisms inside the cell, while regulated activity occurs mainly in the golgi and is dependent on the activity of protein kinase C. Alpha-secretase activity in the golgi is thought to compete directly with the beta-secretase pathway for APP substrates during membrane protein maturation.^[8] Cell-surface cleavage by alpha secretase is very rapid after APP reaches the cell surface.^[9]

The activity of alpha secretases has been implicated in the regulation of learning and memory formation. Release of the APPsα ectodomain has neurotrophic effects that counteract apoptotic signaling and promote synapse formation, processes that are upregulated when ADAM10 is overexpressed.^[10] Alpha secretase activity has also been observed to be upregulated in response to the signaling peptide PACAP.^[11]

Related alpha-secretases, including ADAM10, have also been implicated in similar maturation events for other transmembrane proteins such as MHC class I proteins. Recent evidence suggests that some such proteins are first processed to ectodomains by alpha secretases and subsequently cleaved by another Alzheimer's-associated protease complex, gamma secretase in its presenilin-complexed form. ^[12] The Notch pathway bears many similarities to APP processing and is also regulated in part by ADAM10.^[13]

References

^ Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F. (1999). Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 96(7):3922-7. PMID 10097139
^ Fahrenholz F, Gilbert S, Kojro E, Lammich S, Postina R. (2000). Alpha-secretase activity of the disintegrin metalloprotease ADAM 10. Influences of domain structure. Ann NY Acad Sci 920:215-22. PMID 11193153
^ Detlev Ganten, Aloys Greither : Molekularmedizinische Grundlagen von altersspezifischen Erkrankungen, 2004, Springer-Verlag, ISBN 3-540-00858-6
^ Asai M, Hattori C, Szabo B, Sasagawa N, Maruyama K, Tanuma S, Ishiura S. (2003). Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase. Biochem Biophys Res Commun 301(1):231-5. doi:10.1016/S0006-291X(02)02999-6 PMID 12535668
^ Tanabe C, Hotoda N, Sasagawa N, Sehara-Fujisawa A, Maruyama K, Ishiura S. (2006). ADAM19 is tightly associated with constitutive Alzheimer's disease APP alpha-secretase in A172 cells. Biochem Biophys Res Commun 352(1):111-7. doi:10.1016/j.bbrc.2006.10.181 PMID 17112471
^ Hotoda N, Koike H, Sasagawa N, Ishiura S. (2002). A secreted form of human ADAM9 has an alpha-secretase activity for APP. Biochem Biophys Res Commun 293(2):800-5. doi:10.1016/S0006-291X(02)00302-9 PMID 12054541
^ citation needed
^ Skovronsky DM, Moore DB, Milla ME, Doms RW, Lee VM. (2000). Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network. J Biol Chem 275(4):2568-75. PMID 10644715
^ De Strooper B, Annaert W. (2000). Proteolytic processing and cell biological functions of the amyloid precursor protein. J Cell Sci 113 ( Pt 11):1857-70. PMID 10806097
^ Bell KF, Zheng L, Fahrenholz F, Cuello AC. (2006). ADAM-10 over-expression increases cortical synaptogenesis. Neurobiol Aging Epub. PMID 17187903
^ Kojro E, Postina R, Buro C, Meiringer C, Gehrig-Burger K, Fahrenholz F. (2006). The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein. FASEB J 20(3):512-4. PMID 16401644
^ Carey BW, Kim DY, Kovacs DM. (2007). Presenilin/gamma-secretase and alpha-secretase-like peptidases cleave human MHC Class I proteins. Biochem J 401(1):121-7. PMID 17150042
^ Hartmann D, de Strooper B, Serneels L, Craessaerts K, Herreman A, Annaert W, Umans L, Lubke T, Lena Illert A, von Figura K, Saftig P. (2002). The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. Hum Mol Genet 11(21):2615-24. PMID 12354787

UpToDate Contents

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1. 認知症の予防 prevention of dementia
2. アミロイドーシスの概要 overview of amyloidosis
3. アミロイド疾患の遺伝的要因 genetic factors in the amyloid diseases
4. 汗腺膿瘍（にきび）の病因、臨床的特徴、および診断 pathogenesis clinical features and diagnosis of hidradenitis suppurativa acne inversa
5. アルツハイマー病の遺伝学 genetics of alzheimer disease

English Journal

Honokiol inhibits melanoma stem cells by targeting notch signaling.

Kaushik G1, Venugopal A2, Ramamoorthy P2,3, Standing D2, Subramaniam D2,3, Umar S2,3, Jensen RA4,3, Anant S1,2,3, Mammen JM1,3.
Molecular carcinogenesis.Mol Carcinog.2015 Dec;54(12):1710-21. doi: 10.1002/mc.22242. Epub 2014 Dec 9.
Melanoma is an aggressive disease with limited therapeutic options. Here, we determined the effects of honokiol (HNK), a biphenolic natural compound on melanoma cells and stemness. HNK significantly inhibited melanoma cell proliferation, viability, clonogenicity and induced autophagy. In addition, H
PMID 25491779

A Fluorescent Analog of Batimastat Enables Imaging of α-Secretase in Living Cells.

Leriche G, Chen AC, Kim S, Selkoe DJ, Yang J.
ACS chemical neuroscience.ACS Chem Neurosci.2015 Nov 11. [Epub ahead of print]
The ADAM family of metalloproteases cleave a diverse range of transmembrane substrates, resulting in the release of their soluble ectodomains. This process of protein shedding, termed α-secretase processing, is involved in many facets of both normal and disease related cellular function. While the
PMID 26559179

Serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer's disease.

Bianco OA1, Manzine PR1, Nascimento CM1, Vale FA2, Pavarini SC1, Cominetti MR1.
International psychogeriatrics / IPA.Int Psychogeriatr.2015 Nov 11:1-6. [Epub ahead of print]
BACKGROUND: Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic an
PMID 26555131

Japanese Journal

The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments

LAVOIE MJ
J Biol Chem 278, 34427-34437, 2003
NAID 80016232083

Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase

ASAI M.
Biochem. Biophys. Res. Commun. 301, 231-235, 2003
NAID 80015903327

Related Pictures

Alpha Secretase APP processing via alpha-secretase Alpha-Secretase Cleavage of the Amyloid cleaved by either alpha or beta secretase Alpha- and beta-secretase Alpha-secretase Cleaving APP Molecule

★リンクテーブル★

リンク元	「amyloid precursor protein secretase」「αセクレターゼ」「beta-secretase」「gamma-secretase」「α-セクレターゼ」
関連記事	「alpha」「secreta」