USP30 Inhibition Stops Progression of Parkinson’s Disease in Mice – Fight Aging!

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USP30 Inhibition Stops Progression of Parkinson’s Disease in Mice


Parkinson’s disease arises from the spread of misfolded α-synuclein proteins in the nervous system. This produces a wide array of dysfunction, but the most vulnerable cell population to this particular form of neurodegenerative pathology are domaminergenic cells. Their loss provokes the most evident symptoms of the condition. As noted here, this vulnerability appears to have something to do with clearance of damaged mitochondria, and thus with mitochondrial function more generally. Researchers are investigating ways to improve the situation, such as this representative small molecule approach.



Parkinson’s disease is a neurodegenerative disorder caused by the progressive loss of the group of brain cells responsible for producing dopamine, a neurotransmitter that plays a critical role in regulating movement and coordination. As these neurons degenerate and dopamine levels decrease, individuals with Parkinson’s disease experience a wide range of symptoms, including tremors, stiffness, and difficulties with balance and coordination.



Evidence suggests the dopamine-producing cells die off in Parkinson’s disease because something has gone awry with the clearance of the cells’ old and dysfunctional mitochondria – organelles that are the source of cells’ energy, sometimes called the powerhouse of the cell. Researchers focused on an enzyme called USP30 which plays a role in this process. In a mouse model engineered to lack the gene that produces the enzyme – known as a “knockout model” because one specific gene has been deleted for the purposes of experimentation – the researchers observed that the loss of USP30 protected against the development of Parkinson’s-like motor symptoms, increased clearance of damaged mitochondria in neurons, and protected against the loss of dopamine-producing neurons.



In a second set of experiments, the team validated the knockout studies using a proprietary molecule developed by Mission Therapeutics to block the enzyme’s action in the dopamine-producing neurons. As in the knockout mice, inhibiting the enzyme’s action increased clearance of dysfunctional mitochondria and protected dopamine-producing neurons.


Link: https://www.bidmc.org/about-bidmc/news/2023/11/researchers-halt-progression-in-parkinsons-disease-mouse-model

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