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 | ||
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] |