Parkin is an enzyme in cells that tags outer
membrane proteins on damaged mitochondria and
thereby sets off repair or recycling of the damaged
mitochondria. Mutations in the parkin gene which
make it dysfunctional cause Parkinson’s disease in
humans, suggesting this enzyme is key for keeping
susceptible cells healthy. Accordingly, increasing
levels of parkin protects against models of disease
in several animal species, from fruit fly and worm
to non-human primates and human cells.
To maintain homeostasis, there are always opposing forces in living cells. An opposing enzyme to parkin
is USP30, which removes the tags attached by
parkin and slows the repair and recycling
mechanisms. In fruit flies, decreasing USP30 can
offer protection against mitochondrial dysfunction.
We look to translate these breakthrough discoveries
to human medicines by activating parkin or
inhibiting USP30 using small molecules.
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