Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons.

Cell death involving oxidative stress and mitochondrial dysfunction is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson's disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson's disease.

Ergothioneine and mitochondria: An important protective mechanism?

Mitochondrial dysfunction is implicated in a wide range of human disorders including many neurodegenerative and cardiovascular diseases, metabolic diseases, cancers, and respiratory disorders. Studies have suggested the potential of l-ergothioneine (ET), a unique dietary thione, to prevent mitochondrial damage and improve disease outcome. Despite this, no studies have definitively demonstrated uptake of ET into mitochondria.

Hepatocyte-intrinsic SMN deficiency drives metabolic dysfunction and liver steatosis in spinal muscular atrophy.

Spinal Muscular Atrophy (SMA) is typically characterized as a motor neuron disease, but extra-neuronal phenotypes are present in almost every organ in severely affected patients and animal models. Extra-neuronal phenotypes were previously underappreciated as patients with severe SMA phenotypes usually died in infancy; however, with current treatments for motor neurons increasing patient lifespan, impaired function of peripheral organs may develop into significant future comorbidities and lead to new treatment-modified phenotypes. Fatty liver is seen in SMA animal models , but generalizability to patients and whether this is due to hepatocyte-intrinsic Survival Motor Neuron (SMN) protein deficiency and/or subsequent to skeletal muscle denervation is unknown.

Protective Effect of Ergothioneine against 7-Ketocholesterol-Induced Mitochondrial Damage in hCMEC/D3 Human Brain Endothelial Cells.

Recent findings have suggested that the natural compound ergothioneine (ET), which is synthesised by certain fungi and bacteria, has considerable cytoprotective potential. We previously demonstrated the anti-inflammatory effects of ET on 7-ketocholesterol (7KC)-induced endothelial injury in human blood-brain barrier endothelial cells (hCMEC/D3). 7KC is an oxidised form of cholesterol present in atheromatous plaques and the sera of patients with hypercholesterolaemia and diabetes mellitus.

Protective Effect of Ergothioneine Against Stroke in Rodent Models.

Ergothioneine (ET) is a naturally occurring antioxidant and cytoprotective agent that is synthesized by fungi and certain bacteria. Recent studies have shown a beneficial effect of ET on neurological functions, including cognition and animal models of depression. The aim of this study is to elucidate a possible effect of ET in rodent models of stroke.

What Do Randomized Controlled Trials Inform Us About Potential Disease-Modifying Strategies for Parkinson's Disease?

Research advances have shed new insight into cellular pathways contributing to PD pathogenesis and offer increasingly compelling therapeutic targets. In this review, we made a broad survey of the published literature that report possible disease-modifying effects on PD. While there are many studies that demonstrate benefits for various therapies for PD in animal and human studies, we confined our search to human "randomised controlled trials" and with the key words "neuroprotection" or "disease-modifying".