Microtubule affinity-regulating kinase 4 (MARK4) (MARK4)

Microtubule affinity-regulating kinase 4 (MARK4) is a serine/threonine kinase that plays a critical role in regulating microtubule dynamics by phosphorylating microtubule-associated proteins (MAPs), such as tau, MAP2, and MAP4 [3, 15]. This phosphorylation leads to the detachment of MAPs from microtubules, thereby promoting microtubule instability and facilitating cellular processes like mitosis, cell polarity, and ciliogenesis [10, 15]. MARK4 is highly expressed in the brain and is significantly upregulated in Alzheimer's disease, where it contributes to the pathological hyperphosphorylation of tau and the subsequent formation of neurofibrillary tangles [4, 9]. Recent studies have identified the anti-diabetic drug Empagliflozin as a potent inhibitor of MARK4, binding to its kinase domain and inhibiting its activity [2, 5]. This interaction suggests that Empagliflozin may have therapeutic potential beyond glucose regulation, specifically in treating neurodegenerative disorders and certain cancers where MARK4 is overexpressed [6, 7]. Beyond neurodegeneration, MARK4 is implicated in various cancers and the regulation of the NLRP3 inflammasome, making it a versatile therapeutic target [9, 10].

Other names

MAP/microtubule affinity-regulating kinase 4MARKL1PAR-1DKIAA1860MAP/microtubule affinity-regulating kinase-like 1Serine/threonine-protein kinase MARK4

Inhibition of kinase activity; ATP-competitive binding in the kinase domain