TABLE 2.
Summary of morphine-, heroin-, nicotine-, and alcohol-induced neurotoxicity according to their effect on the structural integrity of the BBB and their respective molecular pathways.
| Drugs | Pathways involving in BBB leakiness-gene/proteins of interest | Effect on BBB |
| Morphine | Myosin light chain protein kinases | ↑ |
| P-glycoprotein | ↓ | |
| Reactive oxygen species (ROS) | ↑ | |
| Heroin | Junctional adhesion molecule-2 (JAM-2) | ↑ |
| P-glycoprotein | ↓ | |
| Zonula occludens-1 (ZO-1) | ↓ | |
| Nicotine | Claudin-1 and -5 | N.D. |
| Claudin-3 | ↓ | |
| Junctional adhesion niolecule-l (JAM-1) | ↓ | |
| Nitric oxide (NO) | ↑ | |
| P-glycoprotein | ↓ | |
| Reactive oxygen species (ROS) | ↑ | |
| Zonula occludens-1 (ZO-1) | ↓ | |
| Zonula occludens-2 (ZO-2) | N.D. | |
| Alcohol | ERK1/2 and p-38 | ↑ |
| Matrix metalloproteinase- 9 (MMP-9) | ↑ | |
| Matrix metalloproteinase-3 (MMP-3) | ↑ | |
| Reactive oxygen species (ROS) | ↑ | |
| Toll like receptor- 2 (TLR-2) | ↑ | |
| Toll like receptor-3 (TLR-3) | ↑ | |
| Toll like receptor- 4 (TLR-4) | ↑ | |
| Transient receptor potential cation channel (TRP7) | ↓ |