Table 4.
Natural molecules mitigate excessive ER stress for NDD treatment.
| Compounds | Models | Mechanisms | Administration | Ref. |
|---|---|---|---|---|
| Astragaloside-IV | MPP+-induced MN9D cells; MPTP-induced PD mice | Lessening the expression of CHOP protein by restraining the expression of lincRNA-p21 | i.p. | [54] |
| Berberine | 3 × Tg AD mice or APP/PS1 mice | Reducing Aβ production and ER stress by inhibiting PERK/eIF2α-mediated BACE1 translation | oral | [55,56] |
| Curcumin | ApoE4 transgenic mice as AD model | Inhibiting ER stress by reducing GRP78 and IRE1α expression | i.p. | [57] |
| Echinacoside | 6-OHDA-induced PC12 cells and rats as PD model | Relieving ER stress by promoting seipin degradation and GRP94/BIP-ATF4-CHOP pathway; decreasing ROS accumulation | i.p. | [52] |
| Aβ1-42-induced SH-SY5Y cells; APP/PS1 mice as AD model | Reducing Aβ production and deposition by repressing BACE1 activity; inhibiting ER stress via the PERK/eIF2α pathway | i.g. | [53] | |
| Epigallocatechin Gallate | Aβ1-42-induced SH-SY5Y cells; APP/PS1 mice as AD model | Mitigating ER abnormal ultrastructural swelling; downregulating GRP78, CHOP, cleaved-caspase-12 and -3 expressions | oral | [58] |
| Luteolin | APP23 mice as AD model | Preventing ER stress to suppress microglial activation by suppressing CHOP and IL-1β mRNA levels | i.p. | [59] |
| Quercetin | Okadaic acid-induced SH-SY5Y cells; high fat diet-induced AD mice |
Suppressing ER stress by decreasing phosphorylation of IRE1α and PERK; inhibiting TXNIP and NLRP3 inflammasome activation; attenuating tau phosphorylation | oral | [60] |
| Resveratrol | Rotenone-induced PD rats | Ameliorating ER stress by downregulating CHOP and GRP78 expressions and hampering caspase-3 activity; restoring redox balance by suppressing xanthine oxidase activity and protein carbonyls formation and activating glutathione peroxidase and Nrf2 signaling pathway | i.g. | [61] |
| Tanshinone IIA | APP/PS1 mice as AD model | Preventing abnormal expression of GRP78, eIF2α, IRE1α, ATF6; suppressing the activation of CHOP and JNK pathways | i.p. | [62] |
BACE1: β-site APP cleavage enzyme 1; IRE1α: inositol requiring enzyme-1α; TXNIP: thioredoxin-interacting protein; NLRP3: NOD-, LRR- and pyrin domain-containing protein 3; i.g. for intragastric administration; i.p. for intraperitoneal injection; oral for drugs mixed in the diet.