beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase.
AuthorsWong HK, Sakurai T, Oyama F, Kaneko K, Wada K, Miyazaki H, Kurosawa M, De Strooper B, Saftig P, Nukina N,
JournalJ Biol Chem
PubMed ID15824102
'Sequential processing of amyloid precursor protein (APP) by membrane-bound proteases, BACE1 and gamma-secretase, plays a crucial role in the pathogenesis of Alzheimer disease. Much has been discovered on the properties of these proteases; however, regulatory mechanisms of enzyme-substrate interaction in neurons and their involvement in pathological changes are still not ... More
Positive and negative regulation of the gamma-secretase activity by nicastrin in a murine model.
AuthorsLi J, Fici GJ, Mao CA, Myers RL, Shuang R, Donoho GP, Pauley AM, Himes CS, Qin W, Kola I, Merchant KM, Nye JS,
JournalJ Biol Chem
PubMed ID12815056
Nicastrin is a component of the gamma-secretase complex that has been shown to adhere to presenilin-1 (PS1), Notch, and APP. Here we demonstrate that Nicastrin-deficient mice showed a phenotype that is indistinguishable from PS1/PS2 double knock-out mice, whereas heterozygotes were healthy and viable. Fibroblasts derived from Nicastrin-deficient embryos were unable ... More
Ubiquilin-1 modulates ?-secretase-mediated e-site cleavage in neuronal cells.
AuthorsViswanathan J, Haapasalo A, Kurkinen KM, Natunen T, Mäkinen P, Bertram L, Soininen H, Tanzi RE, Hiltunen M,
Journal
PubMed ID23663107
Ubiquilin-1 is an Alzheimer's disease-associated protein, which is known to modulate amyloid precursor protein (APP) processing, amyloid-ß (Aß) secretion, and presenilin-1 (PS1) accumulation. Here, we aim to elucidate the molecular mechanisms by which full-length transcript variant 1 of ubiquilin-1 (TV1) affects APP processing and ?-secretase function in human neuroblastoma cells ... More