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Compound clogs Plasmodium's in-house garbage disposal, hitting malaria parasite where it hurts

A spoon that's spent some time in a functioning garbage disposal is not a pretty thing to see. But did you see what happened to the garbage disposal?

Stanford microbiologist pathologist Matt Bogyo, PhD, has had his own blades whirring for quite some time in a search for drugs to combat the organism responsible for malaria. This one-celled organism, Plasmodium falciparum, wells in the bodies of more than a billion people, hits 250 million new human targets every year (virtually all of them in developing tropical countries) and kills almost a million (most of them children). And the drugs that have, for years, worked effectively to stall the disease (in those victims fortunate enough to gain access to them) have started to stop working.

That's where the garbage disposals come in. Virtually every living cell, from the ones that singlehandedly compose P. falciparum to the ones in the human body that the parasite is infecting, produce a lot of garbage. So, evolution being more than just another pretty face, all of these cells have in-house garbage disposals called proteasomes. These nano-appliances play a mega role in the everyday life of a cell whether it's sick or healthy. As I wrote last August in a release about a very different topic:

[v]irtually all cells in creatures ranging from yeast to humans contain multitudes of these tiny tube-shaped machines, which suck... defective proteins into their holes and chop them into smithereens.

Suffice it to say that if you're a protein you don't want to fall into one.

All proteasomes - from those in the malaria parasite to those in our bodies - are pretty similar. But they have their differences. Bogyo and his teammates seem to have found a very discriminating molecular spoon: a derivative of a (conveniently) already-on-the-market cancer drug, carfilzomib, that just happens to gum up P. falciparum's garbage disposal, but not ours. The experiments leading to this spoon (a drug, actually) are described in this just-out study in Cell Chemistry & Biology.

Vive la difference!

Previously: Nervous breakdown: Preventing demolition of faulty proteins counters neurodegeneration in lab mice, Taming of the malaria parasite? Study takes us one step closer to vaccine and Malaria protection in wearable form
Photo by SanFranAnnie

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