Proteasome-mediated effects on amyloid precursor protein processing at the γ -secretase site
نویسندگان
چکیده
Fiona FLOOD*, Suzanne MURPHY†, Richard F. COWBURN*, Lars LANNFELT‡, Brian WALKER§ and Janet A. JOHNSTON†1 *Karolinska Institute, Neurotec Department, Division of Experimental Geriatrics, Huddinge, S-14186, Sweden, †Queen’s University, Belfast, School of Biology and Biochemistry, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K., ‡Uppsala University Hospital, Department of Geriatric Medicine, Uppsala, S-75125, Sweden, and §Queen’s University, Belfast, School of Pharmacy, McClay Research Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
منابع مشابه
Generation of Amyloid-β Is Reduced by the Interaction of Calreticulin with Amyloid Precursor Protein, Presenilin and Nicastrin
Dysregulation of the proteolytic processing of amyloid precursor protein by γ-secretase and the ensuing generation of amyloid-β is associated with the pathogenesis of Alzheimer's disease. Thus, the identification of amyloid precursor protein binding proteins involved in regulating processing of amyloid precursor protein by the γ-secretase complex is essential for understanding the mechanisms un...
متن کاملSubstrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site
γ-Secretase generates the peptides of Alzheimer's disease, Aβ(40) and Aβ(42), by cleaving the amyloid precursor protein within its transmembrane domain. γ-Secretase also cleaves numerous other substrates, raising concerns about γ-secretase inhibitor off-target effects. Another important class of drugs, γ-secretase modulators, alter the cleavage site of γ-secretase on amyloid precursor protein, ...
متن کاملInvestigation of the Iron Oxide Nanoparticle Effects on Amyloid Precursor Protein Processing in Hippocampal Cells
Introduction: Iron oxide nanoparticles (Fe2O3-NPs) are small magnetic particles that widely used in different aspects of biology and medicine in modern life. Fe2O3-NP accumulated in the living cells due to absence of active system to excrete the iron ions so damages cellular organelles by highly reactivity. Method: Herein cytotoxic effects of Fe2O3-NP with 50 nm size were investigated on prima...
متن کاملSpecific Inhibition of β-Secretase Processing of the Alzheimer Disease Amyloid Precursor Protein.
Development of disease-modifying therapeutics is urgently needed for treating Alzheimer disease (AD). AD is characterized by toxic β-amyloid (Aβ) peptides produced by β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP). β-secretase inhibitors reduce Aβ levels, but mechanism-based side effects arise because they also inhibit β-cleavage of non-amyloid substrates like Neure...
متن کاملADAM Gene Expression in The Adult CNS and Genetic Aberrations in Cancer Cells
ADAM metalloprotease-disintegrins share a common modular structure of functional domains for proteolytic, cell adhesion, and signaling interactions. The metalloprotease domain of oughly half of the known ADAMs contain an intact consensus metzincin catalytic site, and they are thus thought to function as active metalloproteases. The types of interactions mediated by ADAMs are expressly conspicu...
متن کامل