TY - JOUR
T1 - Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β-peptide 1-42/1-40
AU - Grünberg, Jürgen
AU - Walter, Jochen
AU - Eckman, Chris
AU - Capell, Anja
AU - Schindzielorz, Alice
AU - Younkin, Steven
AU - Mehta, Nitin
AU - Hardy, John
AU - Haass, Christian
PY - 1998/10/5
Y1 - 1998/10/5
N2 - 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.
AB - 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.
KW - Amyloid β-peptide
KW - Familial Alzheimer's disease
KW - Presenilin- 1
KW - Presenilin-2
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U2 - 10.1097/00001756-199810050-00027
DO - 10.1097/00001756-199810050-00027
M3 - Article
C2 - 9831466
AN - SCOPUS:0032487568
SN - 0959-4965
VL - 9
SP - 3293
EP - 3299
JO - NeuroReport
JF - NeuroReport
IS - 14
ER -