Truncated presenilin 2 derived from differentially spliced mRNAs does not affect the ratio of amyloid β‐peptide 1‐42/1‐40
作者:
Jürgen Grünberg,
Jochen Walter,
Chris Eckman,
Anja Capell,
Alice Schindzielorz,
Steven Younkin,
Nitin Mehta,
John Hardy,
Christian Haass,
期刊:
NeuroReport
(OVID Available online 1998)
卷期:
Volume 9,
issue 14
页码: 3293-3299
ISSN:0959-4965
年代: 1998
出版商: OVID
关键词: Amyloid β-peptide;Familial Alzheimer's disease;Presenilin-1;Presenilin-2
数据来源: OVID
摘要:
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 Δexon 3,4) or exons 3, 4, and 8 (PS2 Δexon 3,4,8). 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 amyloidβ-peptide (Aβ). This suggests that point mutations causing AD are gain of function mutations.
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