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Nedd4 family interacting protein 1 (Ndfip1) is an adaptor of Nedd4-family ubiquitin ligases. Experimental results showed that Ndfip1 had a potential neuroprotective effect in neurology diseases. However, the neuroprotective effect and the underlying mechanisms of Ndfip1 in Parkinson's disease (PD) have not yet been fully elucidated. Therefore, in this study, we explored the neuroprotective effect of Ndfip1 against mitochondrial complex I inhibitor rotenone in a human dopaminergic neuroblastoma SH-SY5Y cell line and further elucidated its possible underlying mechanisms. Our results showed that rotenone could induce the up-regulation of α-synuclein (α-syn) in both mRNA and protein levels. The expression of Ndfip1 decreased at 24 h after rotenone treatment. Further study showed that high expression of Ndfip1 could protect SH-SY5Y cells against rotenone-induced neurotoxicity and antagonize the rotenone-induced increase in α-syn protein levels. In addition, high expression of Ndfip1 inhibited rotenone-induced increase in the protein levels of caspase-3 and decrease in tyrosine hydroxylase (TH). Further study showed that Ndfip1 did not affect the protein expression of iron regulatory protein 1 (IRP1), transferrin receptor 1 (TfR1), while antagonized the increase in protein levels of P62 and ferritin L caused by rotenone. Our findings provide specific identification of Ndfip1 proteins to inhibit the increase of α-syn in rotenone-induced SH-SY5Y cells. Ndfip1 might be a new theoretical drug target for the prevention and treatment of PD.

Stable magnetic coordination particles based on π-conjugated 1,2,4-benzotriazinyl radical ligands were synthesized using a sonochemical method.

We report the first demonstration using π-conjugated radicals for reactive oxygen species (ROS) scavenging. The ester-derived 1,2,4-benzotriazinyl monoradical VER and its carboxyl counterpart VAR exhibit typical antiferromagnetic behavior with a thermally populated spin-triplet state. Upon self-assembly with DSPE-PEG1000, VER formed ∼25 nm size nanoparticles (NPs) with good water dispersibility and stability, no obvious aggregation and degradation were observed after storing at ambient environment for 14 days. In contrast, VAR NPs were unstable and visible aggregates appeared on the seventh day. These radical NPs show good biocompatibility, there was almost no decrease in the cell viability after being incubated with either NPs even at a concentration of 100 μg/mL. Importantly, excessive ROS of the studied model RAW264.7 cells was scavenged to normal concentration when incubated with VER NPs, whereas ROS of VAR NPs treated model cells was almost not changed or even increased.