VOLUME | JUN 2022 Targeting the PINK1/Parkin Pathway: Unraveling Activation Challenges!

Imagine you’re on a quest to activate a complex pathway in your body called the PINK1/Parkin pathway. Sounds like a daunting task, right? Scientists have been interested in drugging this pathway to treat Parkinson’s disease, but it turns out that activating the key players, Parkin and PINK1, is not as easy as it seems. This review dives into the challenges faced in activating these targets effectively. It discusses how simply activating Parkin biochemically may not translate to activation within cells. Additionally, attempts to activate PINK1 with certain compounds called kinetin analogs have not shown promising results in animal models. However, there may be hope in activating the mitophagy pathway, which removes dysfunctional mitochondria, using inhibitors of a protein called USP30. Interestingly, another potential way to activate Parkin involves a cellular stress response called the AMPK-ULK1 pathway. The article concludes by mentioning ongoing clinical trials that will test the effectiveness of these different approaches. If you’re curious about the intricate world of Parkinson’s research and how scientists are tackling the challenge of activating the PINK1/Parkin pathway, dive into this fascinating article!