Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β-peptide 1-42/1-40

Jürgen Grünberg, Jochen Walter, Chris Eckman, Anja Capell, Alice Schindzielorz, Steven G Younkin, Nitin Mehta, John Hardy, Christian Haass

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Numerous mutations in the presenilin (PS) genes cause early onset familial Alzheimer's disease (FAD). Here we characterize the expression of two naturally occurring alternative PS2 transcripts which lack either exons 3 and 4 (PS2 Δexon3,4) or exons 3, 4, and 8 (PS2 Δexon3,4,8). These transcripts do not contain the natural initiation codon within exon 3. The transcripts are efficiently translated as N-terminal truncated proteins. These deleted proteins are still able to regulate formation of endogenous PS fragments, indicating that the C-terminal half of the PS2 protein is sufficient for this phenomenon. Although ~50% of the PS1 and both PS2 mutations occur within the N-terminal region lacking in the PS2 Δexon3,4 and PS2 Δexon3,4,8 proteins, expression of these truncated proteins does not affect pathological generation of amyloid β-peptide (Aβ). This suggests that point mutations causing AD are gain of function mutations.

Original languageEnglish (US)
Pages (from-to)3293-3299
Number of pages7
JournalNeuroReport
Volume9
Issue number14
StatePublished - Oct 5 1998

Fingerprint

Presenilin-2
Amyloid
Messenger RNA
Peptides
Presenilins
Exons
Proteins
Mutation
Alzheimer Disease
Initiator Codon
Point Mutation
Genes

Keywords

  • Amyloid β-peptide
  • Familial Alzheimer's disease
  • Presenilin- 1
  • Presenilin-2

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Grünberg, J., Walter, J., Eckman, C., Capell, A., Schindzielorz, A., Younkin, S. G., ... Haass, C. (1998). Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β-peptide 1-42/1-40. NeuroReport, 9(14), 3293-3299.

Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β-peptide 1-42/1-40. / Grünberg, Jürgen; Walter, Jochen; Eckman, Chris; Capell, Anja; Schindzielorz, Alice; Younkin, Steven G; Mehta, Nitin; Hardy, John; Haass, Christian.

In: NeuroReport, Vol. 9, No. 14, 05.10.1998, p. 3293-3299.

Research output: Contribution to journalArticle

Grünberg, J, Walter, J, Eckman, C, Capell, A, Schindzielorz, A, Younkin, SG, Mehta, N, Hardy, J & Haass, C 1998, 'Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β-peptide 1-42/1-40', NeuroReport, vol. 9, no. 14, pp. 3293-3299.
Grünberg J, Walter J, Eckman C, Capell A, Schindzielorz A, Younkin SG et al. Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β-peptide 1-42/1-40. NeuroReport. 1998 Oct 5;9(14):3293-3299.
Grünberg, Jürgen ; Walter, Jochen ; Eckman, Chris ; Capell, Anja ; Schindzielorz, Alice ; Younkin, Steven G ; Mehta, Nitin ; Hardy, John ; Haass, Christian. / Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β-peptide 1-42/1-40. In: NeuroReport. 1998 ; Vol. 9, No. 14. pp. 3293-3299.
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