UCLA researchers in the Department of Neurology have developed highly selective inhibitors of MARK4, aiming to revolutionize the treatment landscape for cancer and neurodegenerative disease through precise molecular targeting.
BACKGROUND: MARK4 (Microtubule Affinity-Regulating Kinase 4) is a serine/threonine kinase from the AMP-activated protein kinase family, playing a pivotal role in microtubule stability and cellular signaling. Its activity influences the phosphorylation of proteins like Tau, which is crucial for neuronal function. Aberrant Tau phosphorylation leads to neurodegeneration. Overexpression and hyperactivation of MARK4 have been linked to the growth, migration, and survival of various cancers, especially gliomas and breast cancers, as well as the hallmark pathology of Alzheimer’s Disease.
INNOVATION: UCLA researchers led by Professor Varghese John have developed novel compounds that selectively inhibit MARK4. These molecules are engineered for high specificity and potency towards MARK4, minimizing off-target effects seen with broader kinase inhibitors. MARK4 inhibitors represent a promising new class of compounds for the treatment of serious diseases such as cancer and neurodegenerative disorders. These inhibitors specifically target MARK4, a kinase involved in cell cycle regulation, microtubule dynamics, and the progression of malignancies and Alzheimer’s disease.