Table 1 Dysregulation of the BBB via phosphorylation or down-regulation of TJ proteins
TJ proteins modifications | Targeted TJ proteins | Signaling pathway | Stimulus / Diseases | References |
|---|---|---|---|---|
Serine/Threonine Phosphorylation | Cld5 (Thr207) | PKA | cAMP | [120] |
|  | Cld5, Occludin and ZO-1 | nPKC-θ / aPKC-ζ | Hypoxia | [121] |
|  | N.D. | cPKC-α, cPKC-βII , aPKC-λ/ζ | HIV-1 gp120 | [122] |
| Â | Cld5 (T207) Occludin (T382/S507) | RhoA/Rho kinase | HIV-1 encephalitis | [123] |
|  | Cld5, Occludin, ZO-1 | RhoA / PKC-α | CCL2 chemokine | [124] |
| Â | Cld5 and Occludin | MLCK | Alcohol / Reactive oxygen species | |
| Â | N.D. | Hypoxia / Reactive oxygen species | [127] | |
Tyrosine Phosphorylation | Occludin | c-Src | Cerebral ischemia | [128] |
| Â | Occludin | N.D. | Glutamate | [129] |
|  | Cld5 | N.D. | TGF-β | [130] |
| Â | ZO-1 | ND | Tyrosine phosphatase inhibition | [131] |
Down-regulation or degradation | Cld5 and Occludin Internalization | Caveolae-dependent endocytosis | CCL2 chemokine | [132] |
|  | Occludin | JNK, p38MAPK | Amyloid-β peptide | [133] |
| Â | Cld5 | ERK1/2 | HIV-1 Tat protein | [134] |
|  | Occludin and ZO-1 distribution | PLC-γ, PI3K/Akt | Hypoxia | [135] |
| Â | Â | N.D. | Â | [136] |
| Â | Cld5 | N.D. | Â | [137] |
| Â | Cld5 and Occludin | VEGFR | VEGF | [138] |
| Â | Cld3 | N.D. | Multiple Sclerosis Glioblastoma multiforme | [41] |
|  | Cld5, Occludin, ZO-1 | nPKC-δ | Cerebral ischemia | [139] |
| Â | Occludin and ZO-1 | MLCK | HTLV-1 | [140] |
| Â | Cld5 and Occludin | RhoA/RhoK | Reactive oxygen species | [141] |