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Pregled bibliografske jedinice broj: 206707

Mutations in APP have independent effects on Abeta and CTFgamma generation


Hećimović, Silva; Wang, J; Martinez, M; Goate, A
Mutations in APP have independent effects on Abeta and CTFgamma generation // Neurobiology of disease, 17 (2004), 205-218 doi:10.1016/j.nbd.2004.04.018 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 206707 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Mutations in APP have independent effects on Abeta and CTFgamma generation

Autori
Hećimović, Silva ; Wang, J ; Martinez, M ; Goate, A

Izvornik
Neurobiology of disease (0969-9961) 17 (2004); 205-218

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Alzheimer's disease ; Amyloid-beta ; CTFgamma ; Dementia ; Gamma-secretase ; Neurodegeneration ; Presenilin

Sažetak
Understanding the molecular mechanism of beta-amyloid (Abeta) generation is crucial for Alzheimer's disease pathogenesis as well as for normal APP function. The transmembrane domain (TM) of APP appears to undergo presenilin-dependent gamma-secretase cleavage at two topologically distinct sites: a site in the middle of the TM domain that is crucial for the generation of Abeta-peptides, and a site close to the cytoplasmic border (S3-like/epsilon site) of the TM domain that leads to production of the APP intracellular domain (CTFgamma/AICD). We demonstrate that, in contrast to the unique effect of familial Alzheimer's disease (FAD) mutations in APP on Abeta42 production, some but not all FAD mutations also affect CTFgamma generation. Furthermore, changes in total CTFgamma levels do not correlate with either an increase or a decrease of any Abeta species, and inhibition of Abeta-peptide formation starting from position +1 (Abeta1-x) does not affect CTFgamma production. These results suggest that cleavage at the gamma40/42- and the S3-like sites can be dissociated, and that APP signaling and Abeta production are not tightly linked.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekti:
0098092
0098093

Ustanove:
Institut "Ruđer Bošković", Zagreb

Citiraj ovu publikaciju

Hećimović, Silva; Wang, J; Martinez, M; Goate, A
Mutations in APP have independent effects on Abeta and CTFgamma generation // Neurobiology of disease, 17 (2004), 205-218 doi:10.1016/j.nbd.2004.04.018 (međunarodna recenzija, članak, znanstveni)
Hećimović, S., Wang, J., Martinez, M. & Goate, A. (2004) Mutations in APP have independent effects on Abeta and CTFgamma generation. Neurobiology of disease, 17, 205-218 doi:10.1016/j.nbd.2004.04.018.
@article{article, year = {2004}, pages = {205-218}, DOI = {10.1016/j.nbd.2004.04.018}, keywords = {Alzheimer's disease, Amyloid-beta, CTFgamma, Dementia, Gamma-secretase, Neurodegeneration, Presenilin}, journal = {Neurobiology of disease}, doi = {10.1016/j.nbd.2004.04.018}, volume = {17}, issn = {0969-9961}, title = {Mutations in APP have independent effects on Abeta and CTFgamma generation}, keyword = {Alzheimer's disease, Amyloid-beta, CTFgamma, Dementia, Gamma-secretase, Neurodegeneration, Presenilin} }
@article{article, year = {2004}, pages = {205-218}, DOI = {10.1016/j.nbd.2004.04.018}, keywords = {Alzheimer's disease, Amyloid-beta, CTFgamma, Dementia, Gamma-secretase, Neurodegeneration, Presenilin}, journal = {Neurobiology of disease}, doi = {10.1016/j.nbd.2004.04.018}, volume = {17}, issn = {0969-9961}, title = {Mutations in APP have independent effects on Abeta and CTFgamma generation}, keyword = {Alzheimer's disease, Amyloid-beta, CTFgamma, Dementia, Gamma-secretase, Neurodegeneration, Presenilin} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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