Defective neurite extension is caused by a mutation in amyloid ?/A4 (A?) protein precursor found in Familial Alzheimer's Disease
✍ Scribed by Li, Hai Ling ;Roch, Jean-Marc ;Sundsmo, Mary ;Otero, Deborah ;Sisodia, Sangram ;Thomas, Ronald ;Saitoh, Tsunao
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 244 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0022-3034
No coin nor oath required. For personal study only.
✦ Synopsis
Clonal central nervous system neu-sAPPa in the CM. Although sAPPa could block the ronal cells, B103, do not synthesize detectable endogeeffect of Ab, sAPPb could not do so under the identinous APP or APLP. B103 cells transfected with both wild-type (B103/APP) and mutant APP construct cal condition, suggesting the importance of the C-ter-(B103/APPDNL) secreted comparable amounts of minal 15-amino acid sequence in sAPPa. Neverthesoluble forms of APP (sAPP). B103/APP cells proless, sAPPa's protective activity required the N-termiduced sAPP and cleaved at amyloid b/A4 (Ab) 16, the nal sequence around RERMS, previously identified to a-secretase site, and B103/APPDNL cells produced be the active domain of sAPPb. The overall effect of sAPPb cleaved at Ab 1, the b-secretase site. B103/ APP mutation which overproduced Ab and sAPPb APPDNL cells developed fewer neurites than B103/ and underproduced sAPPa was a marked decline in APP cells in a serum-free defined medium. Neurite the neurotrophic effect of APP. We suggest that the numbers of parent B103 cells were increased by the disruption of balance between the detrimental effect 50% conditioned medium (CM) from B103/APP cells of Ab and the trophic effect of sAPP may be important but reduced by the CM from B103/APPDNL cells. in the pathogenesis of AD caused by this pathogenic Chemically synthesized Ab at concentration levels APP mutation ᭧ 1997 John Wiley & Sons, Inc. J Neurobiol higher than 1 nM reduced numbers of neurites from 32: 469-480, 1997