Science Daily reports that in a pair of related studies, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown their drug candidates can target biological pathways involved in the destruction of brain cells in Parkinson’s disease.
The studies, published in the Journal of Medicinal Chemistry and Scientific Reports, suggest that it is possible to design highly effective and highly selective (targeted) drug candidates that can protect the function of mitochondria, which provide the cell with energy, ultimately preventing brain cell death.
These drug candidates act on what are known as the JNK (pronounced “junk”) kinases — JNK1, JNK2 and JNK3 — each an enzyme with a unique biological function. JNK is linked to many of the hallmark components of Parkinson’s disease, such as oxidative stress and programmed cell death.
The scientists found that within JNK3, a single amino acid — L144 — was primarily responsible for the high level of JNK3 selectivity. Isoform selectivity can help to limit potential side effects of a drug.
Intriguingly, some recent studies have shown that JNK3 not only plays a central role in brain cell death in Parkinson’s disease, but also in Alzheimer’s disease. LoGrasso and his colleagues also believe their JNK3 drug candidates have potential for treating ALS (Lou Gehrig’s disease).
1. Ke Zheng, Sarah Iqbal, Pamela Hernandez, HaJeung Park, Philip V. LoGrasso, Yangbo Feng. Design and Synthesis of Highly Potent and Isoform Selective JNK3 Inhibitors: SAR Studies on Aminopyrazole Derivatives. Journal of Medicinal Chemistry, 2014; 57 (23): 10013 DOI: 10.1021/jm501256y
2. HaJeung Park, Sarah Iqbal, Pamela Hernandez, Rudy Mora, Ke Zheng, Yangbo Feng, Philip LoGrasso. Structural Basis and Biological Consequences for JNK2/3 Isoform Selective Aminopyrazoles. Scientific Reports, 2015; 5: 8047 DOI: 10.1038/srep08047