Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein

[Mito]

Abstract​

Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as an mTOR-independent autophagy activator. Trehalose-induced autophagy enhanced the clearance of autophagy substrates like mutant huntingtin and the A30P and A53T mutants of alpha-synuclein, associated with Huntington disease (HD) and Parkinson disease (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin together exerted an additive effect on the clearance of these aggregate-prone proteins because of increased autophagic activity. By inducing autophagy, we showed that trehalose also protects cells against subsequent pro-apoptotic insults via the mitochondrial pathway. The dual protective properties of trehalose (as an inducer of autophagy and chemical chaperone) and the combinatorial strategy with rapamycin may be relevant to the treatment of HD and related diseases, where the mutant proteins are autophagy substrates.

Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein - PubMed

Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as...

pubmed.ncbi.nlm.nih.gov

 

[Limon9]

Abstract​

Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as an mTOR-independent autophagy activator. Trehalose-induced autophagy enhanced the clearance of autophagy substrates like mutant huntingtin and the A30P and A53T mutants of alpha-synuclein, associated with Huntington disease (HD) and Parkinson disease (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin together exerted an additive effect on the clearance of these aggregate-prone proteins because of increased autophagic activity. By inducing autophagy, we showed that trehalose also protects cells against subsequent pro-apoptotic insults via the mitochondrial pathway. The dual protective properties of trehalose (as an inducer of autophagy and chemical chaperone) and the combinatorial strategy with rapamycin may be relevant to the treatment of HD and related diseases, where the mutant proteins are autophagy substrates.

Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein - PubMed

Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as...

pubmed.ncbi.nlm.nih.gov

Great! I think Dr. Peat referenced a review article which cited this paper in one of his newsletters. Cooked mushrooms take more effort, but they're more nutritious and in my opinion much more beneficial than the raw carrot.

 

[golder]

I always see Trehalose in skin care products. Is there something that this does uniquely when applied topically?

 

[Mito]

[

I always see Trehalose in skin care products. Is there something that this does uniquely when applied topically?

Trehalose against UVB-induced skin photoaging by suppressing MMP expression and enhancing procollagen I synthesis in HaCaT cells

Ultraviolet radiation B cause photoaging of the skin by enhancing the high expression of matrix metalloproteinases (MMPs) to degrade collagen and inhi…

www.sciencedirect.com

 

[golder]

[

Trehalose against UVB-induced skin photoaging by suppressing MMP expression and enhancing procollagen I synthesis in HaCaT cells

Ultraviolet radiation B cause photoaging of the skin by enhancing the high expression of matrix metalloproteinases (MMPs) to degrade collagen and inhi…

www.sciencedirect.com

Thanks!

 

[UG Krishnamurti]

In a podcast with Danny, Georgi and Ray talked about some animal which could survive some great amounts of radiation because of the trehalose given to the animals, since most of the sugar used inside the cells were trehalose. They talked about how trehalose is useful and will not put you into a reduced state. And Ray said that it has a similar effect as inositol does. He thinks it's because of the structural effect on the water. On simple organisms (he didn't see studies on mammalian cells) the trehalose and inositol (which isn't a sugar but has special arrangement as hydroxyl groups) make it more effective then sugar in stabilizing proteins. In some studies it treats acute depression where nothing has helped before. Ray thought it will be used like pregnenolone and progesterone as something which has an all purpose protective effect. Some studies even showed that it is powerful anti radiation damage factor: It doesn't get burn as fast as sugar or fructose so it can have longer lasting stabilizing effect.

Also in one study they presented some evidence that pathogenic bacteria Clostridium difficile has evolved to metabolize trehalose so that might not be a good thing (But mostly in the presence of infection probably).

 

[Mito]

they presented some evidence that pathogenic bacteria Clostridium difficile has evolved to metabolize trehalose so that might not be a good thing (But mostly in the presence of infection probably).

It seems recent studies show no causal relationship between trehalose consumption and Clostridium difficile.

Is there a causal relationship between trehalose... : Current Opinion in Gastroenterology

c ribotypes of C. difficile harbour mutations or have acquired extra genes that mean these strains can utilize lower concentrations of bioavailable trehalose, providing a competitive metabolic advantage in some CDI animal models. By contrast, evidence has emerged to show that trehalose-induced...

journals.lww.com

 

[UG Krishnamurti]

It seems recent studies show no causal relationship between trehalose consumption and Clostridium difficile.

Is there a causal relationship between trehalose... : Current Opinion in Gastroenterology

c ribotypes of C. difficile harbour mutations or have acquired extra genes that mean these strains can utilize lower concentrations of bioavailable trehalose, providing a competitive metabolic advantage in some CDI animal models. By contrast, evidence has emerged to show that trehalose-induced...

journals.lww.com

Thanks for the update. I had that study in my notes but I didn't research further.