Caffeic acid and resveratrol ameliorate cellular damage in cell and Drosophila models of spinocerebellar ataxia type 3 through upregulation of Nrf2 pathway

New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models

“…Several lines of evidence have suggested that targeting NRF2 could be a potential therapeutic strategy for neurodegenerative diseases [56]. Indeed, agents activating NRF2, such as Gardenia jasminoides, Glycyrrhiza inflata, 3-alkyl luteolin, caffeic acid, and resveratrol are beneficial to different models of polyQ diseases including SCA3, HD, and SBMA [22,30,31,57,58]. Our study results provide evidence of LM-031 as a new NRF2 activator and its potential for treating SCA17 and other polyQ diseases.…”

“…NRF2 activation can mitigate a number of neurodegenerative diseases including HD [28]. We and other researchers have shown that NRF2 expression is impaired in SCA3 and SCA17 models, and agents enhancing NRF2 rescue the phenotypes induced by mutant polyQ [2,22,[29][30][31][32]. Taken together, we planned to examine more compounds that may activate NRF2 in our SCA17 cell models.…”

“…NRF2 is a master regulator of the antioxidant response through regulating the expression of phase II antioxidant and detoxification genes [27]. Both CREB and NRF2 have been shown to suppress polyQ-mediated toxicity in Drosophila [12,31]. As the neuroprotective effects of LM-031 and licochalcone A in Aβ-GFP-expressing SH-SY5Y cells had been linked to CREB and NRF2 pathways [43], we examined the expressions of CREB, pCREB (S133), BCL2, GADD45B, and NRF2 by immunoblotting using specific antibodies.…”

Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

“…Examples of compounds which are mostly investigated for their potential neuroprotective effects include quercetin, kaempferol and myricetin (flavonols) [ 50 , 51 , 52 , 53 , 54 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ], scutellarin, baicalein, and apigenin (flavones) [ 50 , 55 , 56 , 61 , 87 , 88 , 89 , 90 ], catechins, epicatechin, and epigallocatechin gallate (EGCG, flavanols), as well as genistein (isoflavonoid), and silymarin (flavonolignan) [ 63 , 91 , 92 , 93 , 94 , 95 , 96 ]. The stilbene group is best exemplified by resveratrol, a well-known phenolic compound found in red wine, grape, and virgin olive oil, which has shown remarkable neuroprotective and anti-aging properties in a plethora of experimental models [ 50 , 58 , 59 , 65 , 69 , 97 , 98 , 99 , 100 , 101 , 102 ]. Finally, phenolic acids, which can be subdivided into hydroxybenzoic acids (such as syringic and gallic acids) [ 103 ,…”

“…In the last decades, the search for an effective and potentially safe strategy to combat oxidative stress-mediated neuronal damage has increasingly prompted the investigation of naturally occurring compounds as antioxidant agents. The attenuation of oxidative stress by bioactive compounds belonging to different classes of phytochemicals including (i) flavonoids (quercetin, kaempferol and myricetin, scutellarin, baicalin, apigenin, catechins, epigallocatechin, and genistein) [ 52 , 61 , 81 , 82 , 83 , 88 , 94 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 ]; (ii) phenolic acids (syringic, gallic, caffeic, chlorogenic and salvianolic acids, and curcumin) [ 70 , 103 , 104 , 105 , 138 , 139 , 140 , 141 , 142 , 143 ]; (iii) flavonolignans (silymarin) [ 96 ]; (iv) stilbenes (resveratrol) [ 59 , 65 , 97 , 98 , 144 ]; (v) terpenes (bacosides/bacopasides, withanolides, and the carotenoids lutein and zeaxanthin) [ 7 , 110 , 113 , 115 , 145 , 146 , 147 ]; (vi) alkaloids (berberine and caffeine) [ 148 , 149 ]; (vii) glucosinolates (sulforaphane) and polyamines (spermine/spermidine) [ 123 , 124 ,…”