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Table 1 Summary of compounds involved in regulation (activation or inactivation) of autophagy process of neurological diseases

From: The interplay between oxidative stress and autophagy: focus on the development of neurological diseases

Neurological disease

Therapeutic compound

Species/cell lines

Primary contributed mechanisms related to autophagy

Refs

Alzheimer’s disease

Lithium

Various models

Regulation of inositol monophosphatase, GSK-3β, and mTOR

[161]

Hydroxyurea

APP/PS1 mice

Augmentation of the expression of LC3

[162]

Atorvastatin

Aβ1–42- SH-SY5Y

Elevation of the expression of sestrins and LC3-II, alleviation of sirtuins and TPP1

[163]

Ferric-Tannic nanoparticles

In vitro

activation of lysosome

[164]

Curcumin

APP/PS1 double transgenic AD mice

Inhibition of PI3K/Akt/mTOR, an increase of LC3I/II and Beclin1 expression

[165]

Berberine

Three × Tg-AD mice

Augmentation of LC3-II, Beclin-1, hVps34, and Cathepsin-D

[166]

Berberine and Curcumin

Aβ1-42-AD mice

Augmentation of AMPKα phosphorylation and cell autophagy

[65]

Resveratrol

Aβ1–42-induced AD-PC12

Activation of mitophagy due to the abrogation of oxidative stress

[167]

Geniposide

APP/PS1 mice

downregulation of mTOR

[168]

Polydatin

Aβ-induced neuron cytotoxicity

activation of AMPK/mTOR pathway

[169]

Melatonin

AAV-hTauP301L viral vectors and okadaic acid-Tauopathy, mice and human brain tissue

improvement of the autophagy markers comprising p62, LAMP1, and LC3

[170]

α-Tocopherol

Aβ-SH-SY5Y

Regulation of cathepsin-B, -L, -D, syntaxin 17, GABA type A receptor-associated protein, GABA type A receptor-associated protein-like 1; ATG3, ATG4A, ATG4B, myotubularin related protein 3, UV radiation resistance-associated, autophagy and Beclin 1 regulator 1, vacuole membrane protein 1, WDrepeat domain, phosphoinositide interacting 1, WDrepeat domain, phosphoinositide interacting 2, unc-51 like autophagy activating kinase 2

[171]

Oleuropein aglycone

Aβ-AD mice, SH-SY5Y

Induction of AMPK/ULK1, inhibition of mTOR

[172, 173]

Garcinol

Acrylamide-brain of zebrafish larvae

Regulation of cathepsin-B

[174]

Carnosic acid

Aβ 1–42- SH-SY5Y

Increase LC3-II/I ratio, decrease SQSTM1(p62)

[175]

β-asarone

Aβ, PC12 cells

Alleviation of autophagy occurred via Akt/mTOR signaling pathway

[176]

Euxanthone

Aβ1-42-PC12

Augmentation of LC3-II and Beclin1, alleviation of p62

[177]

Oleocanthal

TgSwDI mice

Activation of AMPK/ ULK1 pathway

[178]

Ganoderma lucidum

MPTP-induced PD in mice

Elevation of NIX expression, decrease of LC3-II/LC3-I ratio, regulation of AMPK, mTOR, and ULK1

[179]

Parkinson’s disease

Metformin

In vitro and in vivo

Activation of AMPK and inhibition of α-synuclein

[180]

Sulforaphane

Rotenone-mice, SH-SY5Y

Decrease expression of LC3-II

[181]

Morphine (low dose)

6-OHDA-SH-SY5Y and rats

Augmentation of LC3-II, alleviation of p62

[182]

Manganese nanoparticle

N27 dopaminergic neuronal cells

Improvement of Beclin 1 and LC3

[183]

α-Arbutin

Rotenone-induced PD, SH-SY5Y, drosophila

Modulation of AMPK/p62

[184]

Polydatin

Rotenone or Parkin deficiency-SH-SY5Y

Promotion of ATG5 in a parkin-independent autophagy manner

[185]

Glycyrrhizic acid

6-OHDA and corticosterone-induced PD in SH-SY5Y

Attenuation of α-Syn and p-S1292-LRRK2 proteins expression, upregulation of LC3B II/I and Beclin-1

[186]

α-lipoic acid

6-OHDA-SH-SY5Y cells

blockade AMPK/mTOR signaling pathway

[187]

Icariin

Rotenone-PC12 cells

Regulation of LC3-II, Beclin1, p62

[188]

β-amyrin

6-OHDA- Caenorhabditis elegans

Regulation of LGG-1

[189]

kaempferol

Rotenone- SH-SY5Y

Increase the expression of LC3-II

[190]

Huntington’s disease

Tolfenamic acid

transgenic R6/1 mice

Increase LC3-II/LC3-I ratio, decrease expression of p62

[191]

Liraglutide

mHTT- SK-N-MC cells

Upregulation of the phosphorylation of Thr172-AMPK and LC3-II

[192]

Trehalose

skin biopsies of HD patients

Increase LC3 and LAMP2-A levels

[193]

Resveratrol

polyQ-Htt- SH-SY5Y

restoring ATG4 level, allowing the LC3 lipidation, facilitating polyQ-Htt degradation

[194]

Rutin

Caenorhabditis elegans

Autophagy by activation of protein degradation

[195]

Amyotrophic lateral sclerosis

Riluzole

HeLa cells

Increase the amount of HSF1 regarding the chaperone-mediated autophagy

[196]

p-Coumaric Acid

SOD1mut- N2a cells

increased the level of LC3-II, decrease the protein level of p62

[197]

Cerebral ischemia

Ulinastatin

A variety of models

Inhibition of neuronal autophagy

[198]

Tanshinone IIA

OGD/R- HT-22 cells

Activation of PI3K/Akt/mTOR pathway

[112]

Resveratrol

cerebral ischemia rats

Increase expression of LC3II

[199]

Gabapentin

middle cerebral artery occlusion-rats

Regulation of the PI3K/Akt/mTOR signaling pathway

[200]

Melatonin

I/R-rats, OGD/R-PC12 cells

Reduction of LC3II/LC3I, an increase of p62

[201]

Lycium barbarum polysaccharide

OGD/R- primary hippocampal neurons

Activation of PI3K/Akt/mTOR pathway

[202]

Tetrahydroxystilbene glucoside

middle cerebral artery occlusion-mice

Elevation of Beclin 1 and the LC3BII/I ratio

[203]

Shengmai

Cerebral I/R injury-mice

modulation of the AMPK, mTOR, and JNK pathways, inhibition of Beclin1 and LC3

[204]

Esculetin

transient bilateral typical carotid artery occlusion -treated mice

Regulation of Bnip3, Beclin1, Pink1, parkin, and the LC-3 II/I ratio

[205]

Luteolin

MCAO rat model

Regulation of SIRT3/AMPK/mTOR Signaling Pathway

[106]

Chronic Cerebral Hypoperfusion

Resveratrol

CCH-rats

Regulation of AKT/mTOR Signaling

[206]

Spinal Cord Injury

Omega-3 fatty acids

Rodent models

Increase of LC3-II expression, reduction of p38 MAPK expression

[207]

Calcitriol

laminectomy and spinal cord compression injury-rats

Augmentation of LC3-II and Beclin1, alleviation of p62

[208]

Spinocerebellar ataxia

Caffeic acid and resveratrol

mutant ataxin-3-SK-N-SH-MJD78 cells, Drosophila

Upregulation of p62 expression

[209]

lactulose and melibiose

SCA3 ATXN3/Q75-GFP cell model

Regulation of autophagy

[210]

Neurotoxicity

Methylone and MDPV

β-keto amphetamines-SH-SY5Y cells

Increase expression of LC3-II

[154]