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Full-Text Articles in Molecular and Cellular Neuroscience
Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes
Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes
Dissertations & Theses (Open Access)
Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on …
Functional Role Of Each Component In Gamma Secretase Complex, Chen Hu
Functional Role Of Each Component In Gamma Secretase Complex, Chen Hu
Doctoral Dissertations
Amyloid hypothesis is widely accepted as the centerpiece of Alzheimer’s disease (AD) pathogenesis. It is believed that the accumulation of amyloid beta (Ab) is the major deterministic factor of AD and the most important causative factor is the ratio of Ab42/Ab40. Gamma(g)-secretase defines the length of Ab and is composed of at least four subunits: presenilins (PS1 or PS2), nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer 2 (Pen-2). They have been reported to have different roles in g-secretase. For example, PS were believed as the catalytic components in g-secretase; NCT was recognized as a substrate receptor; Pen-2 was …
Mcp-1 And App Involvement Of Glial Differentiation And Migration Of Neuroprogenitor Cells, Emmanuel Vrotsos
Mcp-1 And App Involvement Of Glial Differentiation And Migration Of Neuroprogenitor Cells, Emmanuel Vrotsos
Electronic Theses and Dissertations
Neuroprogenitor cells are an important resource because of their potential to replace damaged cells in the brain caused by trauma and disease. It is of great importance to better understand which factors influence the differentiation and migration of these cells. Previously it has been reported that neuroprogenitor cells undergoing apoptotic stress have increased levels of Amyloid precursor protein (APP) and increased APP expression results in glial differentiation. APP activity was also shown to be required for staurosporine induced glial differentiation of neuroprogenitor cells. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is expressed during inflammatory. The binding of MCP-1 to …
The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis
The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis
Electronic Theses and Dissertations
Increased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a …