Fig. 9
Schematic description of kinase signaling pathways in Huntington’s disease. mHTT promotes neuronal apoptosis and inflammatory responses by inhibiting ERK and activating the p38, JNK, and IKKβ signaling pathways. It establishes connections with HTT via the MEK/ERK and AKT signaling pathways, regulating neuronal autophagy, neuroprotection, and glucose uptake pathways. In addition to causing DNA damage by itself, mHTT’s aggregation also leads to pancreatic β-cells damage and activation of CDK5 through its interaction with IRS-2. The aberrant activation of CDK5 reduces microtubule stability, which, in turn, contributes to the exacerbation of mHTT pathology. In addition, the activation of the IKKβ signaling pathway by AKT promotes neuroinflammatory responses, while the inhibition of the JNK signaling cascade by AKT hinders cell apoptosis. The regulatory network formed by the mutual activation and inhibition of kinases plays distinct roles in different stages of the HD pathological process. This figure was created with BioRender.com
