Faculty Opinions recommendation of Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity.

By Raphael Kopan. 2003

443 citations recorded by the source corpus.

Subfields: Clinical Biochemistry, Endocrinology, Diabetes and Metabolism, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/263f669860c3ce87e15bbfe317006a03c8a60813

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In Clinical Biochemistry

In Endocrinology, Diabetes and Metabolism

In Psychiatry and Mental health

Citations in the corpus

Genetics of Alzheimer Disease (2010, unknown): “Moreover, knockin mice with missense mutations of the endogenous murine PSEN1 have high Ab42 levels and perform poorly on the object recognition test.114,115 Double PSEN1/APP transgenics have been developed, and these transgenics suggest that PSEN1, APP, and mutations within these genes play a role ”
Trafficking and proteolytic processing of APP. (2012, background): “Presenilin (PS) 1 or PS2 contain the two critical aspartyl residues within TMDs 6 and 7, which are part of the catalytic domain of the aspartyl protease activity of g-secretase (Wolfe et al. 1999).”
The Alzheimer's Disease Mitochondrial Cascade Hypothesis: Progress and Perspectives (2013, background): “By the late 1990's at least three studies reported toxin-induced mitochondrial dysfunction pushes APP processing towards Aβ production [49-51].”
The Structure of the ζζ Transmembrane Dimer Reveals Features Essential for Its Assembly with the T Cell Receptor (2006, unknown): “N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript subunit of γ-secretase and are thought to perform intramembrane peptide-bond hydrolysis through two catalytic aspartic acids buried in the center of neighboring TM domains (Wolfe et al., 1999).”
Presenilin 1 mutants impair the self-renewal and differentiation of adult murine SVZ-neuronal progenitors via cell autonomous mechanisms involving Notch signaling (2010, background): “8-fold in HES1-promoter activity over Proless-Luc reporter activity was detected in cultures transduced with LV-GFP, LVPS1hWT, LV-PS1 E9, LV-PS1M146L, LV-PS1C410Y or LV encoding the catalytically inactive PS1D257A/D385A PS1 polypeptide (Wolfe et al., 1999) (Fig.”
Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers (2006, background): “In humans, familial forms of AD caused by missense mutations in APP or presenilin (the active site component of γ -secretase (Wolfe et al. 1999) lead to severe tau cytopathology (Sudo et al. 2005).”
Amyloid Precursor Protein Processing and Alzheimer’s Disease (2011, background): “PS1 and PS2 contain two aspartyl residues that play crucial roles in intramembranous cleavage; substitutions of these residues (D257 in TM 6 and at D385 in TM 7) reduces cleavage of APP and Notch1 (De Strooper et al. 1999, Wolfe et al. 1999).”
Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. (2002, background): “5-kd fragment is cleaved by presenilin-dependent -secretase to yield A .(2) We measured the protein level and enzymatic activity of BACE, the primary brain -secretase, in brains with AD and control brains to evaluate a role for increased A production in the pathogenesis of AD.”
Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. (2006, background): “We also investigated PS1-D257A (Figure 1A), a mutant that abolishes g-secretase activity of presenilins (Wolfe et al., 1999).”
Alzheimer’s Disease and the β-Amyloid Peptide (2010, unknown): “Although the exact functional roles of each componenthave yet to be fully elucidated, presenilin is believed to form the active site of the aspartyl protease [16,17], and nicastrin likely serves as a substrate docking subunit [18].”