Table 1.

Reported effects of autophagy-enhancing agents in preclinical PD models

	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	[100, 101]
			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	[82, 92, 93]
				6-OHDA and MPP+ treated PC12 cells	[83]
				MPTP mice	[50, 83]
				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	[85, 86]
			Reduced mitochondrial dysfunction	Rotenone-exposed SH-SY5Y cells	[82, 92]
				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	[92, 93]
			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	[108, 109]
			Increased α-syn clearance	PC12 cells overexpressing WT and A53T α-Syn	[104, 106]
				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	[108, 109]
			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	[122, 123]
			Reduced cell death	Mice expressing A53T α-synuclein	[122]
Lysosomes	GCase	Ambroxol	Restoration of lysosomal function; increased GCase activity	GBA1 mutant fibroblasts	[150, 151]
			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]

Abbreviations: Ref reference number, 2-HPβCD 2-Hydroxypropyl-β-cyclodextrin, α-syn α-synuclein, DA dopaminergic, DOPAC 3,4-Dihydroxyphenylacetic acid, ROS reactive oxidative stress, WT wild-type, 6-OHDA 6-hydroxydopamine, MPTP 1-methyl-4-fenyl-1,2,3,6-tetrahydropyridine, UPS ubiquitin-proteasomal system