Generation of amyloid β protein from its precursor is sequence specific
نویسندگان
چکیده
منابع مشابه
Generation of amyloid β protein from its precursor is sequence specific
Cerebral deposition of amyloid p protein (AI~) is an early and critical feature of AIzheimer's disease. Here we analyze the substrate requirements of proteases ("l~-secretases'3 that cleave the I~-amyloid precursor protein (I~APP) at the N-terminus of AI~ (Asp-597 of I~APP6~s) in intact human cells. The cleavage requires a membrane-bound substrate but tolerates shifts in the distance of the hyd...
متن کاملGeneration 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 کاملAmyloid precursor protein mutation E682K at the alternative β-secretase cleavage β′-site increases Aβ generation†
BACE1 cleaves the amyloid precursor protein (APP) at the β-cleavage site (Met(671) -Asp(672) ) to initiate the generation of amyloid peptide Aβ. BACE1 is also known to cleave APP at a much less well-characterized β'-cleavage site (Tyr(681) -Glu(682) ). We describe here the identification of a novel APP mutation E682K located at this β'-site in an early onset Alzheimer's disease (AD) case. Funct...
متن کاملHeterogeneous Association of Alzheimer’s Disease-Linked Amyloid-β and Amyloid-β Protein Precursor with Synapses
Alzheimer's disease (AD) is increasingly viewed as a disease of synapses. Loss of synapses correlates better with cognitive decline than amyloid plaques and neurofibrillary tangles, the hallmark neuropathological lesions of AD. Soluble forms of amyloid-β (Aβ) have emerged as mediators of synapse dysfunction. Aβ binds to, accumulates, and aggregates in synapses. However, the anatomical and neuro...
متن کاملNuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis
Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Neuron
سال: 1995
ISSN: 0896-6273
DOI: 10.1016/0896-6273(95)90323-2