N- Acetyl Glucosamine - increase protein clearance

[Little_apple]

N-acetyl-D-glucosamine kinase binds dynein light chain roadblock 1 and promotes protein aggregate clearance

EDIT: please see PB comment below

nature.com/articles/s41419-...

michaeljfox.org/grant/glyco...

These results suggest that O-GlcNAc may be a cellular strategy to prevent protein aggregation, which could potentially be exploited for treatment.

pnas.org/doi/10.1073/pnas.1...

I’m not sure if this is the same or similar enough to reap the claimed benefits.

[park_bear]

Regarding the first reference, N-acetyl-glucosamine kinase is not the same as N-acetyl-glucosamine: en.wikipedia.org/wiki/N-ace...

The third reference is favorable. However, here is a study that finds N-acetyl-glucosamine unfavorable: faseb.onlinelibrary.wiley.c...

Increased O-GlcNAcylation Attenuates Autophagic Flux, Induces Mitochondrial Dysfunction and Leads to Accumulation of Alpha-Synuclein in Neurons

" found significantly increased O-GlcNAcylation levels in PD brains compared to control. Whether increased O-GlcNAcylation affects neuronal function and survival was then tested in rat primary cortical neurons. We found that thiamet G... significantly increased protein O-GlcNAcylation, decreased autophagic flux, decreased mitochondrial complex IV activities, increased accumulation of mitochondrial peroxynitrite, and led to an increased α-synuclein accumulation. To confirm our results in vivo, ... We found that dnOGA synaptosomes exhibited increased O-GlcNAcylation, decreased mitochondrial function, increased α-synuclein, and accumulation of autophagosomes. Taken together we proposed that a significant increase of O-GlcNAcylation levels in PD brains may contribute to impairment of neuronal bioenergetics and attenuation of autophagic activities and accumulation of α-synuclein."

[Little_apple in reply to park_bear]

what about the MJFF link?

Alpha-synuclein is a sticky protein that clumps in the brains of people with Parkinson's disease (PD). N-acetyl-glucosamine (O-GlcNAc), a sugar-like molecule, can modify (become attached to) alpha-synuclein in a process called glycosylation. This raises the possibility that the number of modifications -- O-GlcNAc molecules attached to a single alpha-synuclein protein -- may, in turn, affect alpha-synuclein clumping. We have used chemical methods to produce alpha-synuclein with one O-GlcNAc modification. We found that this modification can completely block clumping, making alpha-synuclein less toxic in vitro. Finally, we discovered that O-GlcNAc prevents clumping by blocking the entry of new individual alpha-synuclein proteins into a growing clump. Together, these findings indicate that drugs that increase the number of O-GlcNAc modifications could slow the progression of PD.”

The one you linked to is post mortem and rats and mice. MJFF was just a test tube.

The third I posted which was “favorable” is the most recent, Stanford 2018.

Not sure if this deserves further research

[park_bear in reply to Little_apple]

It is okay for what it is but it does not carry the same level of confidence as a study published in a peer-reviewed journal. Be that as it may, we have got conflicting information here. I am in no position to judge which parties have it right. Under these circumstances I could not recommend taking this substance.

[chartist in reply to Little_apple]

Among the many PD fighting effects of melatonin, reducing Asyn excretion and aggregation is on the list :

assets.researchsquare.com/f...

ncbi.nlm.nih.gov/pmc/articl...

Perhaps Melatonin + NAG, may have synergy toward this end.

Art