Intracellular trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations over the past two decades. APP is the precursor to the amyloid beta-protein (Abeta), the 38-43-amino acid residue peptide that is at the heart of the amyloid cascade hypothesis of Alzheimer disease (AD). Tremendous progress has been made since the initial identi...

Background: Amyloid precursor protein (APP) undergoes cleavage under physiological conditions, predominantly by αand γ-secretases, to form the nonpathogenic sAPPα and p3 fragments. By contrast, amyloid-beta (Aβ) is produced via proteolytic cleavage by βand γ-secretases. In Alzheimer’s disease (AD), APP is preferentially processed via the amyloidogenic pathway, producing large amounts of Aβ that...

Multiple recent reports implicate amyloid precursor protein (APP) signaling in the pathogenesis of Alzheimer's disease, but the APP-dependent signaling network involved has not been defined. Here, we report a novel consensus sequence for interaction with the PDZ-1 and PDZ-2 domains of the APP-interacting proteins Mint1, Mint2, and Mint3 (X11alpha, X11beta, and X11gamma), and multiple novel inte...

The possibility to understand the causes and treat the symptoms of Alzheimer's disease patients is still a great challenge. The triggering events leading to the selective neurodegeneration observed in Alzheimer's brains are not completely understood. This lack of understanding of the pathophysiological processes posses an important theoretical challenge for the rational design of pharmacologica...

Alzheimer's disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (...

The amyloid precursor protein (APP) is the parent molecule from which beta-amyloid protein is cleaved and deposits as amyloid fibrils in the senile plaques of Alzheimer's disease. Its primary structure resembles a receptor; however, no ligand has been identified. In growing hippocampal neurons APP is localized to growth cones. APP immunoreactivity was highly enriched in the axons of mature cult...

Our research has concentrated upon the protein lipid modification of BACE [beta-site amyloid precursor protein cleaving enzyme (beta-secretase)], of which very little is currently known. Lipidation influences the production of Abeta (amyloid beta-protein) by promoting the dimerization of BACE.

The metabolism of the amyloid precursor protein (APP) has been extensively investigated because its processing generates the amyloid-β-peptide (Aβ), which is a likely cause of Alzheimer disease. Much prior research has focused on APP processing using transgenic constructs and heterologous cell lines. Work to date in native neuronal cultures suggests that Aβ is produced in very large amounts. We...

p75 neurotrophin receptor (p75) regulates diverse functions, including survival, differentiation, growth, and apoptosis of neurons, through its association with a number of molecules. Accumulating evidence shows that βamyloid precursor protein (APP)–related molecules, which also regulate multiple neuronal functions, interact with p75. APP is cleaved by secretases to generate several proteins in...