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BACKGROUND Retrograde transport of several transmembrane proteins from endosomes to the trans-Golgi network (TGN) occurs via Rab 5-containing endosomes, mediated by clathrin and the recently characterized retromer complex. This complex and one of its putative sorting receptor components, SorLA, were reported to be associated to late onset Alzheimer's(More)
Abeta is proteolytically produced from the Alzheimer's amyloid precursor protein (APP). Major properties attributed to Abeta include neurotoxic effects that contribute to Alzheimer's disease neurodegeneration. However, Abeta can also affect APP processing and trafficking that, in neurons, is anterogradelly transported via microtubules in a(More)
Infertility is a growing concern in modern society, with 30% of cases being due to male factors, namely reduced sperm concentration, decreased motility and abnormal morphology. Sperm cells are highly compartmentalized, almost devoid of transcription and translation consequently processes such as protein phosphorylation provide a key general mechanism for(More)
Amyloid beta (Abeta) contributes to neurodegeneration in Alzheimer's disease and provides a close association between molecular events and pathology, although the underlying molecular mechanisms are unclear. In the work described here, Abeta did not induce amyloid precursor protein (APP) expression, but APP processing/trafficking was markedly affected. In(More)
Alzheimer's amyloid precursor protein (APP) sorting and processing are modulated through signal transduction mechanisms regulated by protein phosphorylation. Notably, protein kinase C (PKC) appears to be an important component in signaling pathways that control APP metabolism. PKCs exist in at least 11 conventional and unconventional isoforms, and PKCalpha(More)
Cellular protein phosphorylation regulates proteolytic processing of the Alzheimer's Amyloid Precursor Protein (APP). This appears to occur both indirectly and directly via APP phosphorylation at residues within cytoplasmic motifs related to targeting and protein-protein interactions. The sorting signal (653)YTSI(656) comprises the S655 residue that can be(More)
The neurotoxic Abeta peptide is derived by proteolytic processing from the Alzheimer's amyloid precursor protein (APP), whose short cytoplasmic domain contains several phosphorylatable amino acids. The latter can be phosphorylated 'in vitro' and 'in vivo,' and in some cases phosphorylation appears to be associated with the disease condition. Using APP-GFP(More)
Reversible protein phosphorylation is a central mechanism regulating many biological functions, and abnormal protein phosphorylation can have a devastating impact on cellular control mechanisms, including a contributing role in neurodegenerative processes. Hence, many promising novel drug development strategies involve targeting protein phosphorylation(More)
It is now widely accepted that abnormal processing of the Alzheimer's amyloid precursor protein (APP) can contribute significantly to Alzheimer's disease (AD). APP can be processed proteolytically to give rise to several fragments, including toxic beta-amyloid (Abeta) fragments that are subsequently deposited as amyloid plaques in brains of AD patients.(More)
Altered metabolism of the Alzheimer's amyloid precursor protein (APP) appears to be a key event in the pathogenesis of Alzheimer's disease (AD), and both altered phosphorylation and oxidative stress appear to affect the production of the toxic Abeta fragment. Our results show that altered processing of APP was observed under conditions of stress induced by(More)