PMID: 9539132Apr 16, 1998Paper

An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos

Neuron
J A DavisP C Wong

Abstract

Mutations in presenilin 1 (PS1) cosegregate with approximately 25% of early onset familial Alzheimer's disease (FAD) pedigrees. A variety of in vitro and in vivo paradigms have established that one mechanism by which PS1 variants cause AD is by elevating the production of highly amyloidogenic Abeta1-42/43 peptides. PS1 is homologous to sel-12, a C. elegans protein that facilitates signaling mediated by the Notch/lin-12 family of receptors. Wild-type human PS1 complements an egg-laying defect in C. elegans lacking sel-12, while FAD-linked PS1 variants exhibit reduced rescue activity. These data suggested that mutant PS1 may cause disease as a result of reduction in PS1 function. To test the function of FAD-linked PS1 in mammals, we examined the ability of the A246E PS1 variant to complement the embryonic lethality and axial skeletal defects in mice lacking PS1. Finally, to examine the influence of reduced PS1 levels on Abeta production, we quantified Abeta1-42/43 peptide levels in PS1 heterozygous null mice (PS1[+/-] mice). We now report that both human wild-type and A246E PS1 efficiently rescue the phenotypes observed in PS1(-/-) embryos, findings consistent with the view that FAD-linked PS1 mutants retain sufficient normal fun...Continue Reading

References

Dec 1, 1992·Nature Genetics·P St George-HyslopD Crapper McLachlan
Sep 1, 1995·Nature Medicine·W WascoD M Kovacs
Apr 14, 1995·Science·S Artavanis-TsakonasM E Fortini
Mar 15, 1994·Genes & Development·P J SwiatekT Gridley
Dec 1, 1995·Human Molecular Genetics·D CampionS Tardieu
Jan 1, 1996·Human Molecular Genetics·M CrutsC Van Broeckhoven
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·D LevitanI Greenwald
Apr 17, 1997·Nature·M Hrabĕ de AngelisA Gossler
Jul 1, 1997·Nature Genetics·T OdaS C Chandrasekharappa
Jul 1, 1997·Nature Medicine·M K LeeS S Sisodia

❮ Previous
Next ❯

Citations

Feb 23, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M E Gurney
Oct 6, 2000·Journal of Neuroscience Research·M NakajimaT Shirasawa
May 25, 2012·Neuroscience Bulletin·Bin YangYan Zhang
Jun 24, 2004·Neurochemistry International·Fiona FloodRichard F Cowburn
Jun 24, 2004·Neurobiology of Aging·Joanna L JankowskyDavid R Borchelt
Jan 22, 2003·Biochemical and Biophysical Research Communications·Sébastien S HébertGeorges Lévesque
Jun 15, 1999·Brain Research. Molecular Brain Research·O BerezovskaB T Hyman
Dec 22, 2000·Neurobiology of Aging·S M JanickiM J Monteiro
Oct 28, 1999·Neurobiology of Aging·S Y Guénette, R E Tanzi
Feb 12, 2000·Progress in Neurobiology·C CzechL Pradier
Oct 12, 2001·Current Opinion in Neurobiology·J WalterC Haass
May 5, 2001·Biomolecular Engineering·J L JankowskyD R Borchelt
Jun 11, 1999·Clinical Genetics·M NishimuraP H St George-Hyslop
Mar 25, 2000·Clinical Genetics·C L Wellington, M R Hayden
Mar 22, 2001·Journal of Neurochemistry·F Checler
May 17, 2000·Proceedings of the National Academy of Sciences of the United States of America·L KulicC Haass
Sep 5, 2008·The Journal of Biological Chemistry·Regina FluhrerChristian Haass
Nov 11, 1999·Genes & Development·D B DonovielA Bernstein
Apr 8, 2011·Science Translational Medicine·David M HoltzmanAlison M Goate
Aug 13, 2010·Journal of Virology·Balasubramanyam KaranamRichard B S Roden
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Wim Annaert, Bart De Strooper
Feb 3, 1999·Annual Review of Genetics·D L PriceS S Sisodia
Jul 27, 2002·Annual Review of Genomics and Human Genetics·Dennis J Selkoe, Marcia B Podlisny
Jul 12, 2007·Neuro-degenerative Diseases·Bianca Van BroeckSamir Kumar-Singh
Jun 20, 2012·Molecular Neurodegeneration·Shaefali P RodgersJoanna L Jankowsky
Jan 1, 2012·Scientifica·Robert C Barber
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·W SongB A Yankner
Jun 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·Peter MastrangeloDavid Westaway
Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tobias MoehlmannHarald Steiner
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·W J RayA M Goate
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·M GrilliE Ongini
Jan 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jie Shen, Raymond J Kelleher
Nov 19, 2009·Brain Structure & Function·Gregory A ElderPatrick R Hof
Aug 28, 2010·International Journal of Alzheimer's Disease·Angèle T Parent, Gopal Thinakaran
Jul 13, 2000·Current Opinion in Genetics & Development·G Weinmaster
Apr 8, 1999·Neuropharmacology·G R Seabrook, T W Rosahl
Aug 26, 2003·FEBS Letters·Sébastien S HébertGeorges Lévesque

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.