Table 2.
Overview of protein kinases interacting with tau protein and their roles in pathology.
| Protein | Roles in Tau Pathology | References |
|---|---|---|
| ABL1 | involved in formation of apoptotic complex | [172] |
| AKT1 | neuroprotective activity; inactivates pro-apoptotic proteins and promotes cell survival | [173] |
| BRSK (1, 2) | unknown role in tau pathology | - |
| CAMK2A | involved in hyperphosphorylation of tau in AD | [174,175] |
| CDK (1, 5) | accelerate tau hyperphosphorylation and formation of NFT; act neuroprotective by apoptosis inhibition | [176,177] |
| CDK2 | inhibits tau-mediated tubulin polymerization by tau phosphorylation | [178] |
| CSNK1 (A1, D) | involved in formation of Aβ; colocalize with NFT, suggesting a role in tau aggregation | [179,180] |
| DYRK1A | overexpressed in AD; facilitates further tau phosphorylation by GSK3B | [181,182] |
| DYRK2 | overexpressed in AD; involved in activation of apoptosis | [181,183] |
| FYN | facilitates formation of NFT by tau hyperphosphorylation; activates PTK2B; potentiates Aβ-induced synapse damage | [184,185,186] |
| GSK3 (A, B) | responsible for hyperphosphorylation of tau; involved in activation of apoptosis; exacerbate tau pathology when activated by Aβ | [187,188,189] |
| CHEK (1, 2) | unknown role in tau pathology | - |
| LCK | it is downregulated in AD; unknown role in tau pathology | [190,191] |
| LRRK2 | contradictory reports: enhances abnormal tau phosphorylation and promote tauopathy or, no impact on tau pathology was shown | [192,193,194,195] |
| MAP2K7 | colocalize with hyperphosphorylated tau; contribute to Aβ accumulation | [196,197] |
| MAPK (1, 3, 8–14) | overactivated in AD; involved in abnormal tau phosphorylation | [198,199] |
| MARK (1–3) | phosphorylate tau aggregates; colocalizes with NFT | [200] |
| MARK4 | phosphorylate tau aggregates; mutation causes tau hyperphosphorylation, aggregation and tau-mediated neurodegeneration; colocalizes with NFT | [200,201] |
| PHKG1 | unknown role in tau pathology | - |
| PKN1 | regulates tau phosphorylation; colocalize with NFT | [202,203] |
| PRKACA | abnormally phosphorylate α-Synuclein-bound tau; facilitates further phosphorylation of tau by GSK3 kinase; colocalize with NFT; important for regulation of alternative splicing of exon 10 in MAPT | [204,205,206,207] |
| PRKC (A, B, E, G, I, Z) | neuroprotective role through inhibition of GSK3 kinase and reduced tau phosphorylation | [208,209] |
| PTK2B | hyperphosphorylates tau; is regulated by FYN kinase; colocalize with pathological tau proteins in brains of AD patients | [185,210] |
| RPS6K (A1, A3, A5, B1) | their attenuation is neuroprotective; possibly upregulate tau translation; contribute to tau aggregation and synapse damage; inhibit apoptosis | [211,212,213] |
| SGK1 | upregulated in AD; enhances tau hyperphosphorylation by GSK3B activation | [214] |
| SIK1 | unknown role in tau pathology | - |
| SRC | unknown role in tau pathology | - |
| SRPK (1, 2) | involved in regulation of alternative splicing of exon 10 in MAPT, where impaired splicing of exon 10 can lead to tauopathy | [215,216] |
| SYK | accumulation of pathological tau proteins cause overactivation of SYK, which further hyperphosphorylates tau and exacerbate pathology; contributes to the neuroinflammation; inhibits autophagic tau degradation; contributes to neuronal loss | [217,218,219] |
| TTBK1 | enhances tau phosphorylation and aggregation; involved in neurodegeneration | [220,221] |