Synapsin 1 promotes Aβ generation via BACE1 modulation


Autoři: Masato Maesako aff001;  Katarzyna M. Zoltowska aff001;  Oksana Berezovska aff001
Působiště autorů: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226368

Souhrn

It has been revealed that β-amyloid (Aβ) is generated and released from the presynaptic terminals in activity-dependent manner. However, molecules modulating the presynaptic Aβ generation remain elusive. Here we test the hypothesis that Synapsin 1 (Syn1) may acts as a modulator of the Aβ production. Using biochemical and Förster resonance energy transfer (FRET)-based imaging approaches we have found that Syn1 knock down decreases, whereas (over)expression of Syn1 in cells increases the Aβ levels. Mechanistically, Syn1 does not seem to affect the activity of Presenilin 1 (PS1)/γ-secretase, PS1 conformation, or the proximity between PS1 and amyloid precursor protein (APP). However, we found that Syn1 is involved in up-regulation of the β-site APP cleaving enzyme 1 (BACE1)/β-secretase activity and increases the APP/BACE1 interaction. Therefore, we conclude that Syn1 may promote Aβ production via the modulation of BACE1.

Klíčová slova:

Alzheimer's disease – Co-immunoprecipitation – Enzyme-linked immunoassays – Fluorescence resonance energy transfer – CHO cells – Neurons – Proteomics – Synaptic vesicles


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