{Reference Type}: Journal Article
{Title}: Characterizing the role of the dark kinome in neurodegenerative disease - A mini review.
{Author}: Axtman AD;
{Journal}: Biochim Biophys Acta Gen Subj
{Volume}: 1865
{Issue}: 12
{Year}: Dec 2021
{Factor}: 4.117
{DOI}: 10.1016/j.bbagen.2021.130014
{Abstract}: Drugs that modulate previously unexplored targets could potentially slow or halt the progression of neurodegenerative diseases. Several candidate proteins lie within the dark kinome, those human kinases that have not been well characterized. Much of the kinome (~80%) remains poorly studied, and these targets likely harbor untapped biological potential.<BR>This review highlights the significance of kinases as mediators of aberrant pathways in neurodegeneration and provides examples of published high-quality small molecules that modulate some of these kinases.<BR>There is a need for continued efforts to develop high-quality chemical tools to illuminate the function of understudied kinases in the brain. Potent and selective small molecules enable accurate pairing of an observed phenotype with a protein target.<BR>The examples discussed herein support the premise that validation of therapeutic hypotheses surrounding kinase targets can be accomplished via small molecules and they can serve as the basis for disease-focused drug development campaigns.