WordNet

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)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/07 18:32:05」(JST)

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Secretases are enzymes that "snip" pieces off a longer protein that is embedded in the cell membrane.

Processing of the amyloid precursor protein

Among other roles in the cell, secretases act on the amyloid precursor protein (APP) to cleave the protein into three fragments. Sequential cleavage by β-secretase (BACE) and γ-secretase produces the amyloid-β peptide fragment that aggregates into clumps called "plaques" in the brains of Alzheimer's disease patients. If α-secretase acts on APP first instead of BACE, no amyloid-β is formed because α-secretase recognizes a target protein sequence closer to the cell surface than BACE. The non-pathogenic middle fragment formed by an α/γ cleavage sequence is called P3.

Structure[edit source | edit]

The structure of the three secretases varies widely.

The α-secretase gene has not been conclusively identified but is believed to be a metalloproteinase.

BACE is a transmembrane protein with an extracellular aspartic acid protease domain.

γ-secretase is actually a protein complex containing presenilin, nicastrin, APH-1, and PEN-2. Presenilin is believed to harbor the protease domain and represents an important example of an uncommon type of protease that cleaves targets within the cell membrane.

Function[edit source | edit]

Besides their involvement in the pathogenesis of Alzheimer's, these proteins also have other functional roles in the cell.

γ-secretase plays a critical role in developmental signalling by the transmembrane receptor Notch, freeing the cytoplasmic tail of Notch to travel to the cell nucleus to act as a transcription factor.

Although BACE cleaves the extracellular domains of several transmembrane proteins, its physiological function remains unknown.

External links[edit source | edit]

Secretase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 認知症の予防 prevention of dementia
2. アミロイド疾患の遺伝的要因 genetic factors in the amyloid diseases
3. アミロイドーシスの概要 an overview of amyloidosis
4. アルツハイマー病の遺伝学 genetics of alzheimer disease
5. 軽度認知機能障害：予後および治療 mild cognitive impairment prognosis and treatment

English Journal

Presenilins: Role in calcium homeostasis.

Honarnejad K, Herms J.SourceDepartment of Translational Brain Research, DZNE - German Center for Neurodegenerative Diseases, Munich, Germany; Center for Neuropathology and Prion Research, Ludwig Maximilian University, Munich, Germany; Graduate School for Systemic Neurosciences (GSN-LMU), Ludwig Maximilian University, Munich, Germany.
The international journal of biochemistry & cell biology.Int J Biochem Cell Biol.2012 Nov;44(11):1983-6. doi: 10.1016/j.biocel.2012.07.019. Epub 2012 Jul 27.
Mutations in presenilins are responsible for the vast majority of early-onset familial Alzheimer's disease cases. Full-length presenilin structure is composed of nine transmembrane domains which are localized on the endoplasmic reticulum membrane. Upon endoproteolytic cleavage, presenilins assemble
PMID 22842534

Notch1 activation contributes to tumor cell growth and proliferation in human hepatocellular carcinoma HepG2 and SMMC7721 cells.

Gao J, Dong Y, Zhang B, Xiong Y, Xu W, Cheng Y, Dai M, Yu Z, Xu H, Zheng G.SourceDepartment of Digestive Diseases, Wuhan General Hospital of Guangzhou Command PLA, Wuhan, Hubei, P.R. China.
International journal of oncology.Int J Oncol.2012 Nov;41(5):1773-81. doi: 10.3892/ijo.2012.1606. Epub 2012 Aug 24.
Notch signaling controls cellular differentiation and proliferation. Recent studies have shown that Notch signaling plays an important role in the carcinogenesis and progression of a growing number of malignant tumors. We investigated the effect of Notch1 activati
PMID 22922832

Japanese Journal

STRUCTURE-ACTIVITY RELATIONSHIPS OF BIFLAVONOIDS FOR β-SECRETASE (BACE-1) INHIBITORY ACTIVITY

Sasaki Hiroaki,Kitoh Yuki,Miki Kazuhiko [他]
Heterocycles : an international journal for reviews and communications in heterocyclic chemistry 85(11), 2749-2756, 2012-11-01
NAID 40019465384

Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects

Hata Saori,Taniguchi Miyako,Piao Yi,Ikeuchi Takeshi,Fagan Anne M.,Holtzman David M.,Bateman Randall,Sohrabi Hamid R.,Martins Ralph N.,Gandy Sam,Urakami Katsuya,Suzuki Toshiharu
Molecular Neurodegeneration 7, 16, 2012-04-25
… Conclusions: We confirm that Aβ40 is the most abundant Aβ species, and we propose a model in which CSF p3-Alcα can serve as a either (1) a nonaggregatable surrogate marker for γ-secretase activity; … We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alcα and Aβ40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of γ-secretase function and/or transmembrane domain peptide clearance. …
NAID 120004710987

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リンク元	「セクレターゼ」「分泌酵素」
拡張検索	「amyloid precursor protein secretase」「beta-secretase」「alpha-secretase」「gamma-secretase」
関連記事	「secreta」