From: Therapeutic potential of autophagy-enhancing agents in Parkinson’s disease
Target | Agent | Main effect | PD model | Ref | |
---|---|---|---|---|---|
mTOR-dependent pathways | AMPK | Metformin | Reduced cell death | Drosophila melanogaster mutated for LRRK2 | [95] |
MPTP mice | [96] | ||||
Reduced phospho-Ser129 α-syn levels | α-Syn overexpressing SH-SY5Y cells | [98] | |||
AMPK | AICAR | Reduced cell death | LRRK2-mutated Drosophila Melanogaster | [95] | |
AMPK (SIRT1) | Resveratrol | Increased α-syn clearance | α-Syn overexpressing PC12 cells | [100] | |
Reduced cell death | Rotenone-exposed SH-SY5Y cells | ||||
Improved mitochondrial functioning | Cultured PARK2-mutant fibroblasts | [102] | |||
Beclin-1 | PREP inhibitor (KYP-2047) | Decreased oligomeric α-syn, increased striatal DA levels | A30P α-syn transgenic mice | [140] | |
Beclin-1 | Isorhynchophylline | Increased α-syn clearance | N2a cells transfected for WT, A53T, and A30P α-Syn; Embryonic DA neurons | [141] | |
Increased α-syn clearance/Reduced α-syn accumulation | WT, A30P, and A53T α-syn expressing PC12 cells | [4] | |||
B103 neuronal cells expressing α-syn and Beclin-1 | [103] | ||||
α-Syn-transgenic mice | [68] | ||||
α-Syn-transgenic rats | [70] | ||||
mTORC1 | Rapamycin and Rp analogues (CCI-779, RAD001 and AP23573) | Reduced phospho-Ser129 α-syn levels | α-Syn overexpressing SH-SY5Y cells | [98] | |
Reduced cell death | Rotenone-exposed SH-SY5Y cells | ||||
6-OHDA and MPP+ treated PC12 cells | [83] | ||||
MPTP mice | |||||
α-Syn-transgenic mice | [68] | ||||
α-Syn-transgenic rats | [70] | ||||
Drosophila melanogaster mutated for PINK-1 and Parkin | [87] | ||||
Improved motor function, reduced synaptic injury | A53T- α-Syn transgenic mice | [84] | |||
Reduced levodopa-induced dyskinesia | 6-OHDA mice; 6-OHDA rats | ||||
Reduced mitochondrial dysfunction | Rotenone-exposed SH-SY5Y cells | ||||
Drosophila melanogaster mutated for PINK-1 and Parkin | [87] | ||||
TFEB | 2-HPβCD | Increased α-syn clearance | H4 human neuroglioma cells transfected for α-syn | [143] | |
mTor-independent pathways | IMPase | Lithium | Increased clearance of A53T and A30P α-syn | PC12 cells expressing A53T and A30P α-syn | [88] |
Reduced apoptosis and mitochondrial dysfunction | Rotenone-exposed SH-SY5Y cells | ||||
Improved motor function, increased viability DA cells in the SN, decreased loss of DOPAC | MPTP mice (combined treatment with lithium and sodium valproate) | [94] | |||
Ins | Sodium Valproate | Reduced apoptosis and mitochondrial dysfunction | Rotenone-exposed SH-SY5Y cells | [92] | |
Improved motor function, increased viability DA cells in the SN, decreased loss of DOPAC | MPTP mice (combined treatment with lithium and sodium valproate) | [94] | |||
Ins | Carbamazepine | Reduced apoptosis and mitochondrial dysfunction | Rotenone-exposed SH-SY5Y cells | [92] | |
SLC2A transporters | Trehalose | Reduced cell loss | Rotenone-treated rats and PC12 cells | [107] | |
MPTP mice; A53T α-Syn overexpressing rats | |||||
Increased α-syn clearance | PC12 cells overexpressing WT and A53T α-Syn | ||||
NB69 human neuroblastoma cells | [105] | ||||
Rotenone-treated PC12 cells | [107] | ||||
A53T α-Syn overexpressing rats | [109] | ||||
Increased clearance of detergent-insoluble α-syn | A53T α-Syn overexpressing mice | [110] | |||
Reduced motor deficits | MPTP mice; A53T α-Syn overexpressing rats | ||||
Reduced neuroinflammation | MPTP mice | [108] | |||
Unknown | SMERs (SMER 10, 18 & 28) | Increased A53T α-syn clearance | PC12 cells expressing A53T α-syn | [112] | |
Unknown | Latrepirdine | Increased α-syn clearance | Saccharomyces cerevisiael, SH-SY5Y cells expressing α-syn and WT mice | [115] | |
Decreased cell death | Saccharomyces cerevisiae expressing α-syn | [115] | |||
Unknown | Spermidine | Reduced motor dysfunction, increased lifespan; Reduced neuronal cell loss | Drosophila melanogaster expressing α-syn; Caenorhabditis elegans expressing α-syn | [118] | |
Unknown (polyphenols) | Curcumin | Reduced α-syn accumulation | SH-SY5Y Cells expressing WT and A53T α-syn | [119] | |
Kaempferol | Reduced ROS, apoptosis, and mitochondrial dysfunction | Rotenone-exposed SH-SY5Y cells, mouse primary neuronal culture | [120] | ||
C. album polyphenol fractions | Reduced α-syn accumulation; reduced ROS | Hu neuroglioma H4 cells expressing αSyn; Yeast cells expressing αSyn | [121] | ||
Unknown | Nilotinib | Increased α-syn clearance; improved motor function | Mice expressing A53T α-synuclein; mouse primary cortical neurons | ||
Reduced cell death | Mice expressing A53T α-synuclein | [122] | |||
Lysosomes | GCase | Ambroxol | Restoration of lysosomal function; increased GCase activity | GBA1 mutant fibroblasts | |
Reduction of oxidative stress | GBA1 mutant fibroblasts | [150] | |||
GCase | Isofagomine | Improved motor performance, increased α-syn clearance, reduced neuroinflammation | WT-α-syn overexpressing mice | [159] | |
Lysosome | Acidic Nanoparticles | Restoration of lysosomal function; reduced DA cell loss | Cultured ATP13A2 and GBA-mutant fibroblasts; MPTP mice | [145] |