Tau-related kinases and tau phosphorylation machinery (Tau kinases) (Tau kinases)

Tau-related kinases and the tau phosphorylation machinery comprise a group of enzymes responsible for the post-translational modification of the microtubule-associated protein tau. Key members of this machinery include glycogen synthase kinase 3 beta (GSK-3β), cyclin-dependent kinase 5 (CDK5), microtubule-affinity regulating kinases (MARK), and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) [PMID: 19428306, PMID: 21907146]. Under physiological conditions, these kinases maintain a balance of tau phosphorylation to regulate microtubule stability and axonal transport. In neurodegenerative diseases known as tauopathies, such as Alzheimer's disease, an imbalance in this machinery leads to tau hyperphosphorylation. This causes tau to detach from microtubules, aggregate into insoluble neurofibrillary tangles, and induce synaptic dysfunction and neuronal death [PMID: 30706333]. Therapeutic strategies targeting these kinases aim to reduce tau hyperphosphorylation and slow disease progression. However, the ubiquitous nature of these kinases and their involvement in diverse signaling pathways, such as Wnt signaling and cell cycle regulation, present significant challenges for achieving drug selectivity and avoiding adverse effects [PMID: 25159931, PMID: 32694780].

Other names

Tau protein kinasesTPKsMicrotubule-associated protein tau kinasesTau-phosphorylating enzymes

Small molecule inhibition of specific kinases within the machinery to reduce the hyperphosphorylation of tau protein, thereby preventing its dissociation from microtubules and subsequent aggregation into neurofibrillary tangles [PMID: 19428306, PMID: 30706333].