Autophagy in Schwann cells: A potential pharmacotherapeutic target in diabetic peripheral neuropathy

Table 1 Targets and agents for preventing diabetic peripheral neuropathy by regulating Schwann cell autophagy

Ref.	Agents	Target	Functions	Dose in vitro
[37]	Lycorine	AMPK/MMP9	Decrease MMP9 expression and induce autophagy (increase)	2.87 μg/mL
[38]	Resveratrol	N/A	Promote autophagy (increase)	10 μM
[25]	Muscone	Akt/mTOR	Inhibit p-AKT/p-mTOR expression and mitigates autophagy (decrease)	10 μm
[40]	Astragaloside IV	MicroRNA-155	Reduce apoptosis by promoting autophagy (increase)	15 μg/mL
[42]	Salvianolic acid B	JNK	Prevent autophagic cell death by activating the JNK pathway (decrease)	0.1-10 μM
[43]	Quercetin	N/A	Alleviate high glucose-induced damage by autophagy (decrease)	25 μM
[45]	Curcumin	Erk1/2 and Akt	Accelerate cell autophagy and prevent cell apoptosis (increase)	30 μM
[46]	Lentinan	AMPK/mTOR	Promote autophagic flux (increase)	100 μg/mL
[48]	Docosahexaenoic acid	AMPK	DHA attenuates excessive autophagy (decrease)	10 μM
[50]	Imidazole propionate	Erk/mTOR	The reduction of imidazole propionate promotes migration of Schwan cells through enhancing autophagy (increase)	100 μM
[51]	Epothilone B	PI3K	Enhance migration and autophagy (increase)	1 nM
[52]	5-azacytidine	TXNIP	Reduce TXNIP protein expression, improve autophagy and inhibite apoptosis (increase)	10 μM
[53]	AG490	STAT3	Enhance P62 expression in high glucose-stimulated RSC96 cells (increase)	N/A
[54]	4’-chlorodiazepam (Ro5- 4864)	Translocator protein	Improve Schwann cells function by activating autophagy (increase)	10-5 M
[57]	Healthy plasma-derived exosomes (miR-20b-3p)	Stat3	Alleviate autophagy impairment (increase)	20 μg/mL
[58]	Exosomes produced by adipose-derived stem cells (miRNA-26b)	Kpna2	Promote the regeneration of the myelin sheath by moderately reducing autophagy (decrease)	50 μg/mL
[60]	Long non-coding RNA XIST	MiR-30d-5p/SIRT1	Induce autophagy (increase)	N/A
[62]	LV-lipin1 overexpressing virus	N/A	Decreased the autophagic hyperactivity and apoptosis (decrease)	1.0 × 109 TU/mL
[64]	Plasmid-UNC5B	AMPK/ULK1	Facilitates autophagic flux in SCs (increase)	N/A
[66]	Methyltransferase-like protein 3	MiR-192-5p/ATG7	Stimulated miR-192-5p maturation to depress ATG7 and SCs autophagy (decrease)	N/A
[70]	Fibroblast growth factor 21	ERK/Nrf-2	Suppresses autophagy-induced cell death (decrease)	250 ng/mL
[71]	Basic fibroblast growth factor	TEFB	Activate autophagy (decrease)	100 ng/mL
[73]	protein inhibitor of activated STAT1	MiR-124	Inhibit apoptosis and promote autophagy of Schwann cells (increase)	N/A
[75]	Triggering receptor expressed on myeloid cells-2	N/A	TREM2 deficiency induces mitochondrial damage and autophagy of Schwann cells (increase)	N/A
[77]	Rat p66shc siRNA	N/A	Recovers the high glucose-induced impairment of autophagy and ER stress in SCs (increase)	N/A
[79]	Mst1 siRNA	N/A	Promoted parkin recruitment to mitochondria in SCs (increase)	N/A

AMPK: Adenosine monophosphate-activated protein kinase; mTOR: Mammalian target of rapamycin; MMP9: Matrix metallopeptidase 9; JNK: C-Jun N-terminal kinase; Erk1/2: Extracellular signal-regulated kinase 1/2; DHA: Docosahexaenoic acid; PI3K: Phosphatidylinositol 3-kinase; TXNIP: Thioredoxin interacting protein; STAT3: Signal transducer and activator of transcription 3; Kpna2: Karyopherin subunit alpha 2; XIST: X-inactive specific transcript; SIRT1: Sirtuin 1; ULK1: Unc-51-like kinase 1; UNC5B: Uncoordinated gene 5 homolog B; ATG7: Autophagy related 7; Nrf-2: Nuclear factor-erythroid 2 related factor 2; TEFB: Transcription elongation factor B; TREM2: Triggering receptor expressed on myeloid cells 2; ER: Endoplasmic reticulum; SCs: Schwann cells; Mst1: Mammalian ste20-like kinase 1; N/A: Not applicable.