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Quantification and distribution of β-secretase alternative splice variants in the rat and human brain

Zohar, Ofer, Cavallaro, Sebastiano, D’Agata, Velia, Alkon, Daniel L.·2003·Molecular Brain Research
DOI 10.1016/s0169-328x(03)00182-7
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Abstract

Beta-amyloid (Abeta) is formed by sequential cleaving of the amyloid precursor protein by two proteolytic enzymes, beta- and gamma-secretases. Beta-secretase (BACE) is a type I transmembrane aspartic proteinase that is highly expressed in the mammalian brain. Four alternative splice variants of BACE are currently known and each encodes for a protein isoform with a different enzymatic activity. In Alzheimer's disease (AD) patients, the enzymatic activity and protein levels of BACE are increased in the neocortex, suggesting their differential expression may have a role in Abeta plaque formation. We have determined the differential expression of BACE mRNA and its splice variants in eight regions of the rat and two of the human brain. In humans, the frontal cortex which shows Abeta deposition in AD, expressed three-fold more BACE than the cerebellum and four fold more than the rats' frontal cortex both of which do not form Abeta plaques. The highest BACE levels of rats were found in the frontal cortex and less in other areas. Although most human and rat brain regions expressed all four BACE variants, the human cerebellum did not express the I-457 BACE variant. Human and rat frontal cortex expressed high levels of the I-501 and I-457 variants, but I-432 was highly expressed only in the rat. Species-specific differences were evident between human and rat brain areas, suggesting that BACE transcript variants may have different evolutionary conservation. Differential expression of BA…

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  • The different BACE1 isoforms have been reported in varying abundance in different tissues and ages.

    “The different isoforms have been reported in varying abundance in different tissues and ages.”

    From BACE1: More than just a β‐secretase (2022) · cites this paper as [71]

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Research works printed but not linked: 21

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Metadata

Authors
Zohar, O., Cavallaro, S., D’Agata, V., & Alkon, D. L.
Venue
Molecular Brain Research
Publisher
Elsevier BV
Published
2003-07
Volume
115
Issue
1
Pages
63-68
ISSN
0169-328X
DOI
10.1016/s0169-328x(03)00182-7
Cited by
30
References
2
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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