Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Amyloid Precursor Protein, Alpha-, Beta- and Gamma-Secretases Expression in Penumbra Cells after Photothrombotic Stroke. Evaluation of the Neuroprotective Effect of Secretase Inhibitors

Version 1 : Received: 11 May 2022 / Approved: 13 May 2022 / Online: 13 May 2022 (08:39:09 CEST)

How to cite: Sharifulina, S.; Guzenko, V.; Logvinov, A.; Khaitin, A.; Kalyuzhnaya, Y.; Dobaeva, N.; Li, Y.; Chen, L.; He, В.; Demyanenko, S. Amyloid Precursor Protein, Alpha-, Beta- and Gamma-Secretases Expression in Penumbra Cells after Photothrombotic Stroke. Evaluation of the Neuroprotective Effect of Secretase Inhibitors. Preprints 2022, 2022050184 (doi: 10.20944/preprints202205.0184.v1). Sharifulina, S.; Guzenko, V.; Logvinov, A.; Khaitin, A.; Kalyuzhnaya, Y.; Dobaeva, N.; Li, Y.; Chen, L.; He, В.; Demyanenko, S. Amyloid Precursor Protein, Alpha-, Beta- and Gamma-Secretases Expression in Penumbra Cells after Photothrombotic Stroke. Evaluation of the Neuroprotective Effect of Secretase Inhibitors. Preprints 2022, 2022050184 (doi: 10.20944/preprints202205.0184.v1).

Abstract

Photothrombotic stroke (PTS) stimulates the level of N- and C-terminal fragments of Amyloid precursor protein (APP) growth in the cytoplasm of ischemic penumbra cells not earlier but at 24 hours. Here we have shown that APP fragments are visualized in thin unmyelinated fibers of neurons, in containing mitochondria large fibers and in synapses but absent in the nuclei. At 24 hours after PTS, some elements of the destroyed tissue accumulated a significant amount of APP protein. The level of ADAM10 α-secretase decreased on the first day after PTS in the rat brain cortex and ADAM-10 co-localized with the lipid raft marker caveolin-1. PTS caused no changes in the level of β-secretase BACE1 either on the first day after PTS or in the early recovery period. The expression of proteins of the γ-secretase complex: presenilin-1 and nicastrin increased in astrocytes, but not in penumbra neurons after PTS. The β-secretase inhibitor LY2886721 did not affect the infarct size of the mouse cerebral cortex and the level of apoptosis of cells in the perifocal region after PTS. Whereas the inhibitor of γ-secretase DAPT reduced the expression of glial fibrillary acidic protein (GFAP) in astrocytes, prevented the growth of apoptosis of mouse cerebral cortex cells reducing the infarct volume on the 7th and 14th days after PTS. DAPT may be considered as a drug for stroke therapy.

Keywords

amyloid precursor protein; photothrombotic stroke; ischemia; alpha-secretase; beta-secretase; gamma-secretase

Subject

LIFE SCIENCES, Molecular Biology

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