Share This Author
Triple-Transgenic Model of Alzheimer's Disease with Plaques and Tangles Intracellular Aβ and Synaptic Dysfunction
A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity
It is reported that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Aβ42 peptide (the 42-residue isoform of the amyloids-β peptide) produced from a variety of cultured cells by as much as 80%.
γ-Secretase Cleavage and Nuclear Localization of ErbB-4 Receptor Tyrosine Kinase
A subsequent cleavage by γ-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus is reported.
An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants.
Human neuroblastoma cells transfected with constructs expressing wild-type beta APP or the beta APP717 mutants linked to familial Alzheimer's disease were compared and it was demonstrated that the 4-kilodalton A beta released from wild- type beta APP is primarily but not exclusively A beta 1-40.
NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo.
R-flurbiprofen reduces Abeta42 levels by targeting gamma-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an Abeta 42 lowering agent.
Production of the Alzheimer amyloid beta protein by normal proteolytic processing.
Human mononuclear leukemic cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta AP derivative essentially identical to the beta AP deposited in Alzheimer's disease.
Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity
- Yong-Jie Zhang, Ya-fei Xu, L. Petrucelli
- BiologyProceedings of the National Academy of Sciences
- 5 May 2009
It is reported that the ectopic expression of a ≈25-kDa TDP-43 fragment corresponding to the C-terminal truncation product of caspase-cleaved T DP-43 leads to the formation of toxic, insoluble, and ubiquitin- and phospho-positive cytoplasmic inclusions within cells.
Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice
Release of excess amyloid beta protein from a mutant amyloid beta protein precursor.
Human neuroblastoma cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared and this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta.
NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
R-flurbiprofen reduces Aβ42 levels by targeting γ-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an A β42 lowering agent.