Parkin, glutamate, NAC, mitophagy

[aspergerian]

Prompted by a new Blaylock paper

and discussion, I browsed the PD glutamate literature and

found Van Laar et al reference describing NAC, parkin, and

excitotoxicity.

Read Van Laar 2015 at: "NAC facilitates Parkin translocation and

mitophagy in neurons following excitotoxic insult – a possible

unexpected role for oxidative stress".

Also read at: "Glutamate exposure causes mitochondrial

depolarization and delayed loss of ATP".

Glutamate excitotoxicity in neurons triggers mitochondrial and

endoplasmic reticulum accumulation of Parkin, and, in the presence

of N-acetyl cysteine, mitophagy.

Van Laar et al 2015,

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

See also:

An update on the potential role of excitotoxicity in the

pathogenesis of Parkinson's disease.

Blandini 2010.

ncbi.nlm.nih.gov/pubmed/209...

Mutant LRRK2 enhances glutamatergic synapse activity and evokes

excitotoxic dendrite degeneration.

ncbi.nlm.nih.gov/pubmed/248...

Neuroprotective and symptomatic effects of targeting group III mGlu

receptors in neurodegenerative disease.

ncbi.nlm.nih.gov/pubmed/242...

[park_bear]

The Van Laar study is contradicted by this clinical study which showed that NAC is beneficial for PWP: journals.plos.org/plosone/a...

[faridaro in reply to park_bear]

Thank you for posting this study - just wish there were more people in both treated and control group.

[aspergerian]

Park Bear,

Thank for posting the additional NAC citation and link. Progress may

occur when seemingly contradictory findings are discussed. NAC remains

in my daily supplement regimen. A potentially important point is

presented in Monti DA et al 2016.

"There are several important limitations to the current study. Although

we randomized patients and included a control group, it was not a

blinded study. It is possible that the improvements that we observed in

the NAC group could be related to the placebo effect due to the use of

the intravenous injection. Studies have documented a relatively strong

placebo effect in Parkinson’s disease patients. For example, in a report

by Goetz et al., 11 studies of medical and surgical interventions for

PD were evaluated [56]. The authors found that the placebo effect in

medication related studies was a mean of 16% with a range from 0–27%.

Surgical interventions had a higher mean placebo response of 42%. Future

studies comparing NAC to a placebo would help to clarify this issue. In

addition...."

[park_bear in reply to aspergerian]

Yes, placebo effect is a big concern. OTOH they got good results in cell culture which is not subject to that.

[faridaro]

Thank you for sharing! I have a number of homozygous variants in GAD which may impair glutamate to GABA conversion, so will have to do more research on NAC.

[BUZZ1397]

Wishing you would summarize using plain language for us non-scientists

[faridaro in reply to BUZZ1397]

Buzz, don't feel bad, we are all here trying to learn the best we can. Here are the highlights of the study:

~ glutamate excitotoxicity in neurons supposedly to have a contributing role in neurodegeneration and PD

~ mitophagy is promoted after glutamate exposure only when the antioxidant N-acetyl cysteine (NAC) is present

Glutamate is excitatory neurotransmitter that is supposed to be converted to GABA (inhibitory neurotransmitter) to keep the right balance of neurotransmitters. I have some genetic variants impairing that process and sometimes feel that my brain is whipped with excess glutamate.

Mitophagy is degradation of mitochondria - powerhouses of the cell which create energy. So, according to this study, this degradation of mitochondria is promoted in the presence of glutamate and NAC, if I understand correctly.

[BUZZ1397 in reply to faridaro]

Glutamate can't be the same substance as glutathione!? I've been taking a Glutathione precursor complex formula for ages which includes 100 mg of NAC. Should I be concerned that it is causing degrading of mitochondria??

[faridaro]

Glutamate is one of the building blocks of glutathione. For a cell to be able to manufacture glutathione it needs three precursors - glutamate, glycine and cysteine. Apparently they have to be in balance, otherwise things can go wrong - have to look into this interplay in more detail, but right now getting ready for a week of vacation and my mind is not in the working mode.

However, some people have tendency to have excess glutamate which is necessary for brain functioning, but too much of which causes cells to get overexcited leading to damage and eventual cell death. Excess can come from overproduction in our bodies and food sources. I always had a headache after eating in Chinese restaurants and eventually realized it was MSG - Monosodium Glutamate. Many food products contain msg - anything that is hydrolyzed and many soy and whey products - isolates and concentrates. Reading food ingredients is my latest hobby...

[999---666 in reply to faridaro]

I recall, people died from this msg....... made from beet sugar, I think.