Table 1.
Table 1. Modulation of neuronal/brain autophagy by antipsychotics.
"Flux" refers to autophagic flux; ↑ denotes increase/activation; ↓ denotes decrease/inhibition; n.a. - not assessed; AMPK - AMP-activated protein kinase; ATG - autophagy related; DA - dopaminergic; PINK1 - Phosphatase and tensin homolog -induced kinase 1; ROS - reactive oxygen species; TDP43 - TAR DNA-binding protein 43; TFEB - transcription factor EB; ULK1 - Unc-51 like autophagy activating kinase.
| Agent | Cells/Tissues | LC3-II | Flux | Mechanisms | Effects | Ref. |
| Pimozide | SH-SY5Y cells | ↑ | ↑ | AMPK/ULK1↑ | Tau clearance; Neuronal spine density↑ | 16 |
| Pimozide | Mouse hippocampus | ↑ | ↑ | AMPK/ULK1↑ | Tau clearance; Memory improvement | 16 |
| Sertindole | SH-SY5Y cells | ↑ | ↑ | ROS↑ | Cell death | 17 |
| Olanzapine | SH-SY5Y cells | ↑ | ↑ | ROS↑; ATG mRNA↑ | Apoptotic death upon autophagy inhibition | 18 |
| Olanzapine | Mouse hippocampus and frontal cortex | ↑ | n.a. | ATG mRNA↑ | Apoptotic death upon autophagy inhibition | 18 |
| Trifluoperazine | SH-SY5Y cells | ↑ | ↑ | TFEB↑; p62 mRNA↑ | n.a. | 19 |
| Trifluoperazine | Deyolked zebrafish lysate | ↑ | ↑ | p62 mRNA↑ | DA neurons rescue in PINK1-/- mutants | 19 |
| Trifluoperazine | Human neurons in vitro | ↑ | ↑ | n.a. | α-synuclein clearance Neuronal survival↑ | 21 |
| Fluphenazine | Rat neurons in vitro | ↑ | ↑ | n.a. | TDP43 clearance; Neuronal survival↑ | 20 |
| Methotrimeprazine | Rat neurons in vitro | ↑ | ↑ | n.a. | TDP43 clearanceM Neuronal survival↑ | 20 |
| Clozapine | Rat frontal cortex | ↑ | n.a. | AMPK/ULK1↑ | n.a. | 23 |
| Clozapine | Rat neurons in vitro | ↓ | ↓ | Autophagosome-lysosome fusion↓ | n.a. | 24 |
| Haloperidol | Rat neurons in vitro | ↓ | ↓ | Autophagosome-lysosome fusion↓ | n.a. | 24 |