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Funded Studies

Parc (a Parkin-related E3 ligase): Functions in Neuronal Survival and Parkinson’s Disease Supplement

Promising Outcomes of Original Grant:
Our research had identified a Parkin-related protein, called Parc, to be important for neuronal survival in situations of mitochondrial injury. Specifically, we found that Parc is important for degrading a toxic protein that is released from damaged mitochondria.  Since Parkin is also important for neuronal survival after mitochondrial injury, we were specifically interested in examining whether Parc and Parkin functioned redundantly. We found that unlike Parkin, Parc was not targeted to the damaged mitochondria, but instead surrounded these damaged mitochondria, allowing it to be in the right place for removing the toxic protein released from damaged mitochondria. Our results also show that the loss of Parc and Parkin together has an outcome that is worse than loss of either protein alone.  These results indicate that Parc and Parkin have distinct but complementary functions.

Objectives for Supplemental Investigation:           
We are most interested in examining how Parc detects and responds to mitochondrial damage in neurons. We have the ability to modulate the precise location of mitochondrial damage in neurons and will investigate how Parc responds in those situations. We will also probe the signals that alert Parc about mitochondrial damage in neurons. Finally, we will examine in detail the consequences of deleting both Parc and Parkin together in pre-clinical models.

Importance of This Research for the Development of a New PD Therapy:      
Our main goals are to investigate how neurons respond to mitochondrial damage and survive. Our research indicates that Parkin and Parc have distinct but complementary functions in this context. Thus, a better understanding of Parc would help develop a therapeutic strategy that ensures optimal neuronal survival for patients with Parkinson’s disease.


Researchers

  • Mohanish Deshmukh, PhD

    Chapel Hill, NC United States


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