Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson's disease model.

ABSTRACT:

Aim

We have previously reported that cambinol (DDL-112), a known inhibitor of neutral sphingomyelinase-2 (nSMase2), suppressed extracellular vesicle (EV)/exosome production in vitro in a cell model and reduced tau seed propagation. The enzyme nSMase2 is involved in the production of exosomes carrying proteopathic seeds and could contribute to cell-to-cell transmission of pathological protein aggregates implicated in neurodegenerative diseases such as Parkinson's disease (PD). Here, we performed in vivo studies to determine if DDL-112 can reduce brain EV/exosome production and proteopathic alpha synuclein (αSyn) spread in a PD mouse model.

Methods

The acute effects of single-dose treatment with DDL-112 on interleukin-1β-induced extracellular vesicle (EV) release in brain tiss

SUBMITTER: Zhu C 

PROVIDER: S-EPMC8056538 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature