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BAP31 deficiency contributes to the formation of amyloid‐β plaques in Alzheimer's disease by reducing the stability of RTN3
Author(s) -
Wang Tianyi,
Chen Jing,
Hou Yue,
Yu Yang,
Wang Bing
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801702r
Subject(s) - chemistry , hippocampus , bace1 as , amyloid (mycology) , presenilin , hippocampal formation , amyloid precursor protein , genetically modified mouse , transgene , microbiology and biotechnology , p3 peptide , alzheimer's disease , biochemistry , neuroscience , biology , medicine , disease , gene , inorganic chemistry
Reticulon (RTN) 3 reduces amyloid‐β (Aβ) plaques (APs) by negative modulation of β‐secretase 1 (BACE1) activity. However, RTN3 aggregates easily, which offsets RTN3's inhibitory effect on BACE1 activity and exacerbates AP deposition. We found that BAP31 was a binding partner of RTN3 and positively correlated with the expression level of RTN3. To further explore how BAP31 is involved in Alzheimer's disease (AD), conditional knockout mice with targeted BAP31 deletion (B‐KO) in the hippocampus and cerebral cortex were generated and hybridized with amyloid precursor protein (APP) PS1 transgenic (AD model) mice to obtain B‐KO‐AD mice. BAP31 knock out in primary hippocampal neurons decreased RTN3 monomer availability and enhanced the level of RTN3 aggregates, indicating that BAP31 deficiency increases the instability of RTN3. More importantly, these effects contributed to BACE1‐mediated APP processing and were responsible for the increased APs in the hippocampus and cerebral cortex of B‐KO‐AD mice. Thus, elevated expression of BAP31 in the human brain is likely to reduce the formation of both RTN3 aggregates and Aβ by enhancing the stability of RTN3.—Wang, T., Chen, J., Hou, Y., Yu, Y., Wang, B. BAP31 deficiency contributes to the formation of amyloid‐β plaques in Alzheimer's disease by reducing the stability of RTN3. FASEB J. 33, 4936–4946 (2019). www.fasebj.org