Waking up dormant dopaminergic neurons to reverse Parkinson's disease

[Farooqji]

Led by Dr. C. Justin Lee along with Dr. Hoon Ryu and Dr. Sang Ryong Jeon, researchers at the Center for Cognition and Sociality within the Institute for Basic Science (IBS), Korea Institute of Science and Technology (KIST), and Asan Medical Center (AMC) have discovered a new mechanism for PD pathology. The researchers reported that the symptoms of PD begin when dopaminergic neurons are "non-functional," even before they die off. Though the neuronal death had been until now believed to be the obvious cause of PD, the study found that the movement abnormalities of PD begin in the earlier stage when dopaminergic neurons, though being alive, cannot synthesize dopamine (in a dormant state).

"Everyone has been so trapped in the conventional idea of the neuronal death as the single cause of PD. That hampers efforts to investigate roles of other neuronal activities, such as surrounding astrocytes," said Dr. C. Justin Lee, the corresponding author of the study. Lee adds, "The neuronal death ruled out any possibility to reverse PD. Since dormant neurons can be awakened to resume their production capability, this finding will allow us to give PD patients hope to live a new life without PD."

medicalxpress.com/news/2020...

[Cons10s]

The link is broken.

[park_bear in reply to Cons10s]

Worked for me, but in any case here is the link to the original research:

cell.com/current-biology/fu...

[pvw2]

Does anyone understand what we can do to awaken dormant dopaminergic neurons?

[Hidden in reply to pvw2]

Micro dosing of certain naturally occurring psychedelic compounds is a promising process. psychologytoday.com/ca/blog...

[jimcaster in reply to pvw2]

The article seems to suggest that MAO-B inhibitors (like Xadago) might help. " Furthermore, they revealed that these neurons could be awakened by treatment with MAO-B inhibitors, which block astrocytic GABA synthesis. The awakening of dormant dopaminergic neurons leads to a significant alleviation of PD motor symptoms."

[pvw2 in reply to jimcaster]

Great; my neurologist has me on rasaginline, which is also a MAO-B inhibitor. I read that way to fast, and MAO-B inhibitor didn't ring a bell at the time. Safinamide , selegiline , and rasagiline are MAO-B inhibitors.

[Zella23 in reply to jimcaster]

My husband has just started with Rasigiline, a couple of months ago and had to cut down the dose from 1mg to a half a 1 mg dose as they certainly improved the C/L response.

He had increased dyskinesia after a C/L dose so after a week cut down to .5mgs as well as cutting out 2 Modopar a day.

He now seems to be doing better hardly any dyskinesia and foot and leg dystonia and he says on a couple of days less fatigue.

He does take supplements and has now added in a sublingual B12.

Not sure what has made the difference but we ll keep going on it! Also been to the gym twice this week with a bit more enthusiasm.

[Xenos in reply to pvw2]

It's written in the paper :

Heo et al. report that astrocytic GABA- mediated aberrant tonic inhibition of DA neurons leads to a reduction in TH expression and dopamine production, causing dormant DA neurons and motor deficits. Blocking astrocytic GABA synthesis by MAO-B inhibition or optogenetic activation of dormant DA neurons reverses PD pathology.

IMAO-Bs would be the solution...

How come I take Rasagiline and do not heal ?

[pvw2 in reply to Xenos]

I don't think it's a fast process, especially at the common prescription dosages. The side effects of higher dosages would probably require around the clock monitoring.

[Xenos in reply to pvw2]

You must be right

[pvw2 in reply to Xenos]

Are your PD symptoms getting worse while on rasagiline?

[Xenos in reply to pvw2]

No, pvw2, it simply makes no difference at all. I take 1 mg rasagiline and up to 4x 50 mg L-Dopa IR per day.

[pvw2 in reply to Xenos]

If it stops your PD symptoms from getting worse and you have been taking it long enough to tell, it may be working. Just stopping PD from progressing is significant.

[Xenos in reply to pvw2]

Let's hope, pvw2. But so many people are taking rasagiline that we would know by now.

[pvw2 in reply to Xenos]

Taking 1 mg x1/day of rasaginline and 0.5 mg x3/day of pramipexole. But, have only taken for 6 months. Symptoms haven't gotten worse, but too early to tell. It would be interesting to hear from others taking rasaginline.

[pvw2 in reply to Xenos]

I started a new question about MAO-B inhibitors, so that it's not buried here.

[PDGal4 in reply to pvw2]

I have responded there. Thanks.

[Parkinsonjisung]

If you read the paper, it states that current Mao-b drugs are not effective for humans at enabling this mechanism:

"These discrepancies can be fully explained by our very recent findings that long-term use of the irreversible MAO-B inhibitors undesirably turns on the compensatory mechanisms for GABA production through an increase in the expression and activity of an alternative GABA-synthesizing enzyme, diamine oxidase"

It does mention a new mao-b drug that they're testing that may work.

cell.com/current-biology/fu...

[Gioc in reply to Parkinsonjisung]

The new mao -b drug is this:

advances.sciencemag.org/con...

[JohnPepper]

I have done just that. Fast walking produces a natural substance called GDNF in the brain, which repairs the damaged brain cells and reverses our Pd symptoms so that we can lead a normal life again/

Look at my website - reverseparkinsons.net and contact me. I will help you to do the same; if your really want to get better.

[LAJ12345]

Blackcurrent juice has maoi inhibitor in it. Maybe try that first. You don’t need a prescription for it at least!

barkers.co.nz/latest-news/h...

“

Note from Barker’s: Barker’s Blackadder Blackcurrant Juice is known to contain Mono-Amine Oxidase (MA0) inhibitors which is why it is thought to be so useful in protecting and supporting healthy brain function. However these same inhibitors (found in some antidepressants) can interfere with certain medications so people being treated for conditions such as Parkinsons, should consult their medical professional before consuming Blackadder Blackcurrant Juice. It is unknown if these same MA0 inhibitors are present in other blackcurrant varieties so if the medication you are on has a warning to avoid taking MA0 inhibiting products, the safest approach is to avoid consuming any varieties of blackcurrants. “

ncbi.nlm.nih.gov/pubmed/302...

“These data provide a clear time course of the reversible inhibition of MAO-B after the single consumption of a of New Zealand "Blackadder" blackcurrant juice standardised at 500 mg of polyphenols and, therefore, provide a therapeutic window on which to base future nutritional interventions.”