I think that it's possible but unlikely that loperamide is having a unique effect, because (a) they've shown that it's operating via the ATF4 mechanism, which is the same mechanism we see in other opioids (and multiple other drugs), and (b) loperamide's activity has generally been pretty well characterized and it doesn't really stand out (it's by no means a new drug - I remember taking it as a generic twenty years ago.)
I'll admit it's possible in the broad sense because ATF4 isn't some super-specific pathway. It's a stress response signal. So while I think (b) above makes a unique mechanism unlikely, (a) by itself isn't a slam-dunk - there are a lot of stress signals that induce cell death when they get amped up enough, and can inhibit cell death if blocked off.
It could also be because they are seeing the ATF4 pathway light up (seaching for keys under the lamppost) and there's some side pathway that is molecule-specific, that is synergistic for the molecule's mechanism of action.
just playing devil's advocate for the paper -- I happen to agree with witty's original comment thesis (except for the argument based on the authority of the journal it was published in)
I think that it's possible but unlikely that loperamide is having a unique effect, because (a) they've shown that it's operating via the ATF4 mechanism, which is the same mechanism we see in other opioids (and multiple other drugs), and (b) loperamide's activity has generally been pretty well characterized and it doesn't really stand out (it's by no means a new drug - I remember taking it as a generic twenty years ago.)
I'll admit it's possible in the broad sense because ATF4 isn't some super-specific pathway. It's a stress response signal. So while I think (b) above makes a unique mechanism unlikely, (a) by itself isn't a slam-dunk - there are a lot of stress signals that induce cell death when they get amped up enough, and can inhibit cell death if blocked off.