An Australian study has questioned the potential of the KTP molecule as a treatment for Parkinson’s disease, challenging the belief held for over a decade. The study, titled “Interaction of PINK1 with nucleotides and kinetin,” published in Scientific Advances, reveals that KTP cannot activate PINK1, a protein crucial for maintaining mitochondrial health, due to its inability to physically bind to it.
According to the Parkinson’s Disease Research Centre at the Walter and Eliza Hall Institute of Medical Research (WEHI), the molecule, previously considered a potential drug candidate for Parkinson’s disease, is too large to function as proposed by the press release.
The study’s co-author, Sylvie Callegari, PhD, a senior research officer at WEHI, emphasized the significance of using advanced imaging to visualize the detailed workings of therapeutic compounds.
PINK1, the protein affected by mutations linked to familial Parkinson’s disease, relies on adenosine triphosphate (ATP) as its energy source. Previous studies had suggested that KTP might also serve as an alternative energy source for PINK1, making it a promising therapeutic candidate for Parkinson’s. However, the new research indicates that KTP is unable to provide energy to PINK1 due to physical constraints.
The study employed cryo-electron microscopy to delve into the molecular structure of PINK1, revealing that KTP is incompatible with the protein’s ATP-binding pocket. The researchers identified a “gatekeeper” amino acid that obstructs the binding of KTP, rendering it ineffective.
The findings contradict over a decade of research, which hinted at kinetin’s ability to activate PINK1 through KTP conversion. However, the study suggests that kinetin may trigger PINK1 via an alternative mechanism, warranting further investigation into potential compounds to activate or stabilize PINK1 for developing new Parkinson’s treatments.
