Drug Classification Target pathology PSI (Z-Ile-Glu(OtBu)-Ala-Leu-al) Reversible β5 inhibitor PD [132] AD [133] Epoxomicin Irreversible β5=β2> β1 inhibitor PD [134]     HD [135] Lactacystin/Clasto-lactacystin β-lactone Irreversible β5=β2= β1 inhibitor PD [2] AD [136] HD [137] ALS [138-141] Autism [109,118] MG101 or ALLN (N-acetyl-Leu-Leu-Norleu-al) Reversible β5 inhibitor PD [142] AD [143] MG115 (Z-Leu-Leu-Nva-al) Reversible β5 and β1 inhibitor PD and AD [144] MG132 (Z-Leu-Leu-Leu-al) Covalently binds to the active site of the β subunits PD [142] ALS [145] Autism [109,118] AD [133,136] MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride) Mitochondrial Complex I inhibitor PD [144,146] PDTC (Pyrrolidine dithiocarbamate) NF-κB inhibitor, antioxidant, immunoproteasome inhibitor ALS [105] Clioquinol 20S inhibitor (Cu-mediated interaction) HD [147] Cyclosporin A Non-competitive β5 inhibitor PD [148,149] Paraquat (pesticide) 20S inhibitor PD [124,150,151] Betulinic acid β5 activator Autism [118] Benzamil Inhibition of acid-sensing ion channels (ASIC1a) HD [126]

Table 1: Proteasome modulators in neurodegenerative disorders. Proteasome inhibitors (unshaded rows) have been mostly employed to create models of neurodegenerative diseases, whereas proteasome activators (shaded rows) have been tested for therapeutic application in neurodegeneration.