Post-Translational Modifications of BACE1 in Alzheimer's Disease

Curr Neuropharmacol. 2022;20(1):211-222. doi: 10.2174/1570159X19666210121163224.

Abstract

Beta-Amyloid Cleaving Enzyme1 (BACE1) is a monospecific enzyme for the key ratelimiting step in the synthesis of beta-amyloid(Aβ) from cleavage of amyloid precursor protein (APP), to form senile plaques and causes cognitive dysfunction in Alzheimer's disease (AD). Post-translation modifications of BACE1, such as acetylation, glycosylation, palmitoylation, phosphorylation, play a crucial role in the trafficking and maturation process of BACE1. The study of BACE1 is of great importance not only for understanding the formation of toxic Aβ but also for the development of an effective therapeutic target for the treatment of AD. This paper review recent advances in the studies about BACE1, with focuses being paid to the relationship of Aβ, BACE1 with posttranslational regulation of BACE1. In addition, we specially reviewed studies about the compounds that can be used to affect post-translational regulation of BACE1 or regulate BACE1 in the literature, which can be used for subsequent research on whether BACE1 is a post-translationally modified drug.

Keywords: APP; Alzheimer`s disease; Aβ; BACE1; neurodegenerative diseases; post-translational modification.

MeSH terms

  • Alzheimer Disease*
  • Amyloid Precursor Protein Secretases*
  • Amyloid beta-Peptides
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Humans
  • Protein Processing, Post-Translational

Substances

  • Amyloid beta-Peptides
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human