June 24, 2024

New Study Disproves Previous Findings on Potential Parkinson’s Disease Target

A recent study conducted by the Walter and Eliza Hall Institute (WEHI) has discovered that a molecule once hailed as a potential drug candidate for Parkinson’s disease is no longer an effective therapeutic option. The research, led by Dr. Zhong Yan Gan, Dr. Sylvie Callegari, and Professor David Komander, has debunked over a decade of previous research that suggested a specific “activator molecule” could enhance the activity of a protein called PINK1, which is linked to early-onset Parkinson’s disease.

Published in the journal Science Advances, the study provides new insights into how PINK1 interacts with natural chemicals and reveals that it cannot interact with larger drug candidates that were previously reported to have similar binding properties. This research has transformed our understanding of PINK1 and will inform future efforts to develop treatments for Parkinson’s disease, which currently has no cure.

Parkinson’s disease is a progressive neurodegenerative disorder that affects around 220,000 people in Australia alone. It is characterized by the degeneration of neurons in the brain, leading to symptoms such as tremors, stiffness, and impaired balance and coordination. While there is currently no cure for Parkinson’s disease, researchers believe that by focusing on early-onset cases and the genetic mutations associated with the disease, they can develop more effective drug therapies.

PINK1 is a mitochondrial protein that plays a vital role in supporting cell survival. When PINK1 is mutated, it loses its ability to function properly. Mitochondria, often referred to as the powerhouses of cells, produce adenosine triphosphate (ATP), which is the main source of energy for cells. When mitochondria are damaged and need to be disposed of, PINK1 tags them for degradation, ensuring the health of the cell.

Understanding the pathways involved in the processing of damaged mitochondria is crucial for developing drug therapies for Parkinson’s disease, and research into PINK1 is one such pathway. In this study, the researchers used high-powered microscopy to visualize PINK1 at an atomic level. They observed how the protein switches into its active form when ATP or a similar molecule called KTP is added.

Over a decade ago, it was reported that KTP could enhance PINK1 activity in cells, making it a promising strategy for early-onset Parkinson’s disease treatment. However, the research team discovered that KTP could not bind to the protein as previously believed. This finding overturns previous assumptions and highlights the need for further investigation into the stabilization of PINK1 on mitochondria and its activation in response to mitochondrial damage.

Dr. Callegari, a senior researcher in the Komander Lab, emphasized the importance of understanding the activation of PINK1 in identifying mitochondrial damage. While there is still much to learn about this process, the researchers know that ATP plays a critical role in activating PINK1 and generating the damage signal.

This groundbreaking study provides valuable insights into the mechanisms of PINK1 and highlights the challenges researchers face in developing effective drug therapies for Parkinson’s disease. Although the potential drug candidate has been ruled out, this research brings us one step closer to finding treatments that can slow, stop, or prevent the progression of this devastating neurodegenerative disorder. Continued research into PINK1 and other pathways involved in Parkinson’s disease will undoubtedly lead to new therapeutic possibilities in the future.

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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it