Previous studies have shown that cathepsins control amyloid beta (Abeta) levels in chromaffin cells via a regulated secretory pathway. In the present study, this concept was extended to investigations in primary hippocampal neurons to test whether Abeta release was coregulated by cathepsins and electrical activity, proposed components of a regulated secretory pathway. Inhibition of cathepsin B ...

specific functions. Notch itself is a single-pass transTwo seemingly unrelated avenues of research, Alzheimembrane receptor with large extracellular and intracelmer’s disease and developmental cell fate specification, lular domains (Figure 1A). During receptor maturation, have intersected at the presenilin and Notch genes. ReNotch is cleaved in its extracellular domain by furin or a cent report...

Proteolytic processing of the amyloid precursor protein (APP) by the β- and γ-secretases releases the amyloid-β peptide (Aβ), which deposits in senile plaques and contributes to the etiology of Alzheimer's disease (AD). The α-secretase cleaves APP in the Aβ peptide sequence to generate soluble APPα (sAPPα). Upregulation of α-secretase activity through the 5-hydroxytryptamine 4 (5-HT4) receptor ...

The proteolytic processing of the amyloidprotein precursor plays a key role in the development of Alzheimer’s disease. Cleavage of the amyloidprotein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving and -secretase, liberates amyloidprotein, a protein associated with the neurodegeneration seen in Alzheimer’s disease. Th...

Abstract Alzheimer’s disease (AD) is a neurodegenerative that inevitably results in dementia and death. Currently, there are no pathogenetically grounded methods for the prevention treatment of AD, all current regimens symptomatic unable to significantly delay development dementia. The accumulation β-amyloid peptide (Aβ), which spontaneous, aggregation-prone, neurotoxic product processing signa...

D i s s e r t a t i o n zur Erlangung des akademischen Grades des Doktors der Naturwissenschaften d o c t o r r e r u m n a t u r a l i u m Summary Alzheimer disease (AD) is the most common form of neurodegenerative diseases. Only little is known about the control mechanisms which affect APP metabolism and that cause Alzheimer´s Disease. Gene expression profiling studies revealed reduced levels...

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of ...

Altered proteolysis of amyloid precursor protein is an important determinant of pathology development in Alzheimer's disease. Here, we describe the detection of two novel fragments of amyloid precursor protein in H4 neuroglioma cells undergoing apoptosis. Immunoreactivity of these 25-35 kDa fragments to two different amyloid precursor protein antibodies suggests that they contain the amyloid-β ...