Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

Abstract

The abnormal accumulation of β‐amyloid peptide (Aβ) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aβ‐mediated neurotoxicity remain elusive, Aβ has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione‐derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET’s potential to counteract Aβ‐toxicity in transgenic Caenorhabditis elegans overexpressing a human Aβ peptide. The accumulation of Aβ in this model leads to paralysis and premature death. We show that ET dose‐dependently reduces Aβ‐oligomerization and extends the lifespan and healthspan of the nematodes.

The biology of ergothioneine, an antioxidant nutraceutical

“…Probably such antioxidant activities are at the core of its biological benefits. Caenorhabditis elegans Protection from amyloid-β-induced cell death (521) Cell injury Rat pheochromocytoma cells Methylglyoxal challenge (573) Cell proliferation K562 cells Involvement of SLC22A4 (418) Caco-2 cells Involvement of SLC22A4 (429) Diabetic embryopathy Rats ERG reduced it to control levels (574) DNA damage in mitochondria HeLa, RAW 264•7, HaCaT, PC12 cells siRNA knockdown of SLC22A4…”

“…Note, however, that at least one mushroom trial indicated no measurable benefits in healthy young physical education students (514) . Brain and serum ERG levels are also markedly different in Parkinson's disease (515) , reviewed in Hang et al (516) , Shao & Le (517) and Shah & Duda (518) , and even in sudden infant death syndrome (519) , and ERG has been shown to be protective against β-amyloid-induced neuronal injury (520) and cytotoxicity (521) . It can also act as an antidepressant (522) .…”

“…It can also act as an antidepressant (522) . The evidence for this comes from direct studies (520) and feeding experiments (522) in mice, as well as via the reduction of β-amyloid peptide in a transgenic C. elegans model (521) . As mentioned above, SLC22A4 polymorphisms are associated with ischaemic stroke (417) .…”

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

“…Moreover, studies have suggested that ET is preferentially accumulated in tissues predisposed to oxidative stress and inflammation and may even be concentrated at sites of tissue injury by cellular modulation of the levels of OCTN1 [ 24 , 32 , 56 , 57 ]. These unique capabilities of ET, which have been reported in a wide range of studies in cells, animal models, and also population studies, suggest that the cytoprotective abilities of ET may be helpful against disorders such as dementia [ 58 , 59 , 60 ], depression [ 61 ], atherosclerosis [ 45 , 46 ], cardiovascular disorders [ 46 , 62 , 63 , 64 ], nonalcoholic fatty liver disease [ 56 ], preeclampsia [ 65 , 66 ], ischemia-reperfusion injury [ 39 , 50 , 67 ], and, especially relevant in this case, ARDS [ 68 ]. This list is by no means exhaustive, with new applications for ET constantly being identified even in other areas of human health, such as improving the efficacy of cancer vaccines [ 69 ] and protection against chemotherapy-induced peripheral neuropathy [ 70 ].…”

“…ET has been shown to be protective against a range of neurotoxins in both in vitro and in vivo models, such as amyloid-β [ 58 , 59 , 183 ], cisplatin [ 184 ], D-galactose-induced dementia [ 185 ], and N -methyl-D-aspartate-induced cytotoxicity in rat retinal neurons [ 186 ]. Moreover, preclinical studies have revealed that ET preserved dopaminergic neurons and motor function in a 6-hydroxydopamine murine model of PD (manuscript in preparation).…”