Mitophagy in neurological disorders

Table 1 Pharmacological regulation of autophagy/mitophagy in neurological diseases

Disease	Drug	Target	Model	Function
AD	UA/AC	AMPK	iPSC neurons	Inhibit mitochondrial fission, increase ATP production ↑
AD	rapamycin	mTOR	PDAPP mice	Inhibits mTOR activity ↑
PD	TFEB	LAMP1	nigra neurons	Induces autophagosome and lysosome biogenesis
HD	PINK1	Parkin	Drosophila	Inhibits accumulation of mitochondria ↑
ALS	Atg1	mTOR	Drosophila	Positively regulates the initiation of autophagy
Stroke	Melatonin	LC3, PINK1	SAH rat	Inhibits dysfunctional mitochondria ↑
Stroke	BNIP3 Silencing	LC3	I/H mice	Inhibits excessive mitophagy
HIE	3-MA	LC3II, p62	HIBI rat	Inhibits autophagy flux
HIE	Glycine	p-AMPK	HI rat	Downregulates AMPK to alleviate autophagy flux ↓
HIE	IPC	p-AMPK	pMCAO rat	Activates AMPK to induce autophagy
HIE	AG	miR-30d-5p	HI rat	Inhibits autophagy^a
HIE	AT	miR-30d-5p	HI rat	Enhance autophagy
Epilepsy	rapamycin	mTORC	TSC mouse	Inhibits S6 phosphorylation ↑
TBI	Morin	LC3II/I, Beclin-1	TBI rat	Augments autophagy
TBI	NIX	LC3II/I, p62	TBI rat	Increases autophagy
TBI	17-AAG	LC3II, Beclin-1	TBI rat	Induces autophagy
TBI	Wnt3α	β-proteasomal	TBI mouse	Activates Wnt/β-catenin pathway ↑

AD, Alzheimer's disease; UA/AC, urolithinA/actinonin; AMPK, AMP-activated protein kinase; iPSC, induced pluripotent stem cell; ATP, Adenosine Triphosphate; mTOR, mechanistic target of rapamycin complex; PD, Parkinson’s disease; TFEB, transcription factor EB; LAMP1, lysosome-associated membrane protein1; HD, Huntington's disease; PINK1, PTEN-induced putative kinase 1; LC3, light chain 3; SAH, subarachnoid hemorrhage; BNIP3, B-cell lymphoma 2 kilodalton interacting protein 3; I/H, ischemia/hypoxia; HIE, hypoxic–ischemic encephalopathy; 3-MA, 3-methyladenine; HIBI, hypoxic–ischemic brain injury; p-AMPK, phosphorylation of AMPK; HI, hypoxia–ischemia; IPC, ischemic preconditioning; pMCAO, permanent middle cerebral artery osslusion; AG, Agomir; AT, Antagomir; TSC, tuberous sclerosis complex; TBI, Traumatic brain injury
^aHarmful to disease; ↑ Up-regulate autophagy/mitophagy; ↓ Down-regulate autophagy/mitophagy.

ISSN: 1742-2094