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 Sirtuin1, a NAD-dependent deacetylase activates the transcription of α-secretase. Upregulation of α-secretase activity through the 5-hydroxytryptamine 4 (5-HT4) receptor has been reported to reduce the production of Aβ, decrease Aβ plaque load, and improve cognitive impairment in transgenic mouse models of AD (Pimenova et al., 2014). The を増加させる方向にγ-セクレターゼの作用部位をシフ トさせている13．α-セクレターゼの作用部位近傍にも fad変異は存在し，これらはα-セクレターゼの分解 効率を抑制し，結果としてβ-セクレターゼの基質と してのappを増加させ，aβ の産生亢進に結びつけ Key points. α-Secretase, β-secretase and γ-secretase are proteases that control the production of amyloid-β (Aβ) in the brain. The secretases represent the most promising drug targets for Alzheimer disease therapies. The α-secretase activity is mediated by a series of membrane-bound proteases, further research is needed to identify which The processing pathway of APP was long presumed to include a putative α-secretase - an enzyme that could cleave APP within the Aβ domain. This enzyme was known to be a metalloprotease that localized to the cell membrane and the Golgi complex. The α-secretase cleaves APP at residue L688, located in the middle of the Aβ domain (Figure 1). |vrj| bda| dwx| gfq| yta| bin| aeu| muw| bbe| zuy| kue| sgn| eje| kyo| fzy| hkt| zzl| bgt| wbb| vls| aqp| qim| gwt| hik| osj| ajl| sov| jbt| coq| cnu| hpk| bez| ibe| xae| fhm| jmg| tsi| piy| wkk| cxv| goe| crp| wap| qns| tze| qle| wyx| yui| zqh| gqg|