Table 3.
Lysosomal reagents or genetic modifications in regulating RN and relevant diseases.
| Name | Target | State | Diseases/model | Result | Effect on injury |
|---|---|---|---|---|---|
| Desipramine | (−) ASM | In vitro | TB infection | Reduced susceptibility to necroptosis | Reduce bacterial burdens, making zebrafish hyperresistant295 |
| ALLN | (−) Calpain | In vitro and in vivo | IRI in hippocampal neurons | (−) Necrosis | Neuroprotection101 |
| In vitro | IRI in lung | (−) Necroptosis | (−) Cell death after IRI in lung135 | ||
| Calpastatin overexpression | Endogenous calpain inhibitor | In vitro and in vivo | (−) Caspase-independent neuronal cell death | Neuroprotection296 | |
| DPI | (−) NOX | In vitro | Human umbilical vein endothelial cells | (−) Apoptosis and necroptosis | ND297 |
| GKT137831 Nox4 siRNA | (−) NOX4 | In vitro | (−) Apoptosis and necroptosis | ND297 | |
| N-Acetyl-l-cysteine | (−) ROS | In vitro | Bupivacaine-induced cytotoxicity of IVD cells | (−) LMP and necroptosis | Reduced cytotoxity30 |
| CDDO | (−) HSP90 | In vitro | (−) Ferroptosis and necroptosis | ND54 | |
| CQ, NH4Cl, and Baf-A1 | Lysosome inhibitor | In vitro | (−) Ferroptosis | ND54 | |
| Baf-A1 and CQ | Lysosome inhibitor | In vitro | In certain cancer cells (e.g., HT1080 and BJeLR) | Can't modulate ferroptosis | ND16 |
| In vitro | MEFs and HT1080 cells | (−) Ferroptosis | ND214 | ||
| Baf-A1 | Lysosome inhibitor | In vitro | PDAC | (−) Ferroptosis | ND190 |
| In vitro and in vivo | Cytosolic flagellin stimulated macrophages | (−) Pyroptosis | ND64 | ||
| Lysosomal lumen alkalizer-CQ | Lysosome inhibitor | In vitro and in vivo | Liver fibrosis | Impair ferritinophagy and ferroptosis | Inhibited anti-fibrosis function of artesunate25 |
| LLME | Lysosomal disrupter | In vitro | AMD | (+) Pyroptosis | ND242 |
| In vitro | Acutely inflamed joints of gout | (+) NETosis | ND77 | ||
| In vitro and in vivo | murine BMDC | (+) Pyroptosis | ND262 | ||
| Ca074Me | (−) Cat B | In vivo | Ischemic injury of hippocampus | Inhibit 67% of programmed necrosis | Neuroprotection33 |
| In vitro and in vivo | endotoxemia | (−) Pyroptosis | ND73 | ||
| In vitro | SH-SY5Y and C6 cells | Partially prevented pyroptosis | ND254 | ||
| in vitro and in vivo | CLP sepsis | (−) Pyroptosis | Attenuate inflammatory responses71 | ||
| In vitro | KUP5 cells and macrophages | (−) Pyroptosis | ND57 | ||
| In vitro | (−) Necroptosis | ND298 | |||
| In vitro | Promyelocytic leukemia cells | (−) Necroptosis | ND299 | ||
| In vitro | PDAC | (−) Ferroptosis | ND190 | ||
| In vitro | Cancer stem cells | (−) Ferroptosis | ND49 | ||
| Genetic knockout of CatB | (−) Cat B | In vitro and in vivo | Coxsackievirus B3-induced viral myocarditis | (−) Pyroptosis | Attenuate243 |
| Genetic deletion of cystatin C | (+) Cat B | In vitro and in vivo | (+) Pyroptosis | Aggravate243 | |
| Ca074Me and pepstatin A | (−) Cats B and D | In vitro | Bupivacaine-induced cytotoxicity of IVD cells | (−) Necroptosis | Reduced cytotoxity30 |
| In vitro | ARPE-19 cells | (−) Apoptosis and pyroptosis | ND259 | ||
| In vitro | Mn2+ exposed BV-2 cells | Prevented a ∼13% parthanatos | Alleviates toxicity74 | ||
| In vitro and in vivo | Cytosolic flagellin stimulated macrophages | Halved pyroptosis | ND64 | ||
| Ca074Me/pepstatin A alone | (−) Cat B or D | In vitro and in vivo | Cytosolic flagellin stimulated macrophages | No effect on pyroptosis | ND64 |
| Ca074Me and Z-FY(t-Bu)FMK | (−) Cats B and L | In vitro | Tamoxifen treated human RPE cells | (−) Apoptosis, necroptosis, pyroptosis | ND246 |
(−): Inhibit; (+): promote; CAD: cationic amphiphilic drugs; MDR: multidrug resistance; TB: tuberculosis; DPI: diphenyleneiodonium; IRI: ischemia–reperfusion injury; IVD: intervertebral disc; Cat: cathepsin; (A)RPE cells: (acute) retinal pigment epithelial cells; CLP: cecal ligation and puncture; AMD: age-related macular degeneration; BMDC: bone marrow-derived dendritic cells; ND: not determined.