Lysosome-autophagy dysfunction contribute to TDCIPP induced Aβ1-42 production in N2a-APPswe cells.

ABSTRACT: Alzheimer's disease is the most common form of dementia characterized on cognitive impairment. Autophagy-lysosome dysfunction is linked to AD pathology. Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardants with the potential to induce neuronal damage. We found that TDCIPP significantly increased expression of BACE1 and of Aβ42. TMT labeled proteomic study were used to reveal profile changes of N2a-APPswe cells after exposure by TDCIPP. Proteomic and bioinformatic analysis revealed that lysosomal proteins were dysregulated after TDCIPP treatment in N2a-APPswe cells. LC3, P62, CTSD, and LAMP1 were increased, while STAT1 was decreased after TDCIPP exposure and dysregulated proteins were validated by Western blotting. Our results, for the first time revealed that TDCIPP could be one of potential environment risk factors for AD development. Autophagy dysregulation may take an important role on TDCIPP induced Aβ42 production.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Benhong Xu  

LAB HEAD: Benhong Xu

PROVIDER: PXD042789 | Pride | 2024-05-24

REPOSITORIES: Pride