PGC1a, insulin, mitochondria and PD

There are many treatments that are supposed to help with PD, but we can't really, accurately, explain why:
- exercise is proving to be very good, but so far I've only found suggestions that it increases BDNF.
- fasting, or calorie restriction has many reports of helping PD. What's that about?
- creatine, a bodybuilding supplement, is in stage III clinical trials as being neuroprotective in PD.
- coconut oil has long been rumoured to help.

What might all these things have in common?

As I'm sure many of us do, I was browsing the neurotalk PD forum, and came across this post:
Biosignatures in blood panel show insulin is key factor in PD

which was most interesting, as I was beginning to get into the theory of insulin and PD myself (especially following the newscientist article a while back suggesting Alzheimer's could / should be renamed Type III diabetes), and my own experiences of hypoglycaemia pre-PD diagnosis.

Here's some other links that got me thinking:

Insulin resistance prevents cells getting sufficient glucose, impacting brain function.

But what could cause insulin resistance? A lack of PGC1a, it seems:

and a lack of PGC1a also causes mitochondrial dysfunction (same links above). And what does mitochondrial dysfunction cause? More insulin resistance, excess free radicals, and more mitochondrial dysfunction. A vicious circle.

In summary: not enough PGC1a -> mitochondrial dysfunction + insulin resistance (and free radicals) -> brain cell energy deficiency -> more mitochondrial dysfunction -> protein amyloid buildup -> neuron death -> dopamine deficiency

So where do the treatments above fit in? Well it seems, reading the articles above, that exercise and fasting both increase PGC1a expression. Creatine helps with production of energy for cells (which dysfunctional mitochondria are struggling to produce enough of):

and coconut oil, with its medium-chain fatty acids, provides an easily utilised alternative fuel for the brain than glucose:

and all the anti-oxidants we keep hearing about that are good for PD, are because they soak up the free radicals caused by the mitochondrial dysfunction, interrupting that vicious cycle. So all the treatments are focused on improving, replacing or supplementing one part of the long chain that could result in PD.

My conclusion from all this? None of the treatments above are in any way bad for you. So it can't possibly hurt to apply them all (exercise, fasting, creatine, anti-oxidants etc) in the hope it somewhat slows down the progression, and in the meantime, wait for medical science to perfect the gene therapy that fixes the root cause, PGC1a deficiency:

Apologies for the quality of some of the links, they're only there to illustrate the basic points. There's plenty of other pages that say similar things with varying amounts of scientific credibility :smile:

One last thought: doesn't this make our neurologists, with their fixation on only the very last part of this chain (dopamine deficiency) look incredibly short sighted? It's like having a car that's constantly leaking oil, and instead of asking why, focusing all your energy on different ways to top the oil up. In fact, it makes me incredibly angry!
Mmj.........thanks for that and in particular for leading us to the biomarker paper studying alternative splicing in blood. It is a beautiful piece of work. I look forward to studies showing whether the regulatory network the biomarkers for PD belong to (and apparently diabetes II) is causing or promoting the disease or is an effect of it.

In your scheme, what do you consider is causing the lack of PGC1a ? How do you account for progression of the disease in the brain?
Could you tell me what PGC1a stands for please? T hanks samdog
PGC-1 α (Peroxisome proliferator-activated receptor gamma coactivator
1-alpha) activates transcription factors which switch on networks of genes.

"Importantly, genes under the control of the master regulator PGC-1 α were under expressed in Parkinson's tissue and neurons isolated from Parkinson's Substantia nigra compared to controls. To test the impact of PGC-1 α a series of experiments were carried out in primary rat neurons in culture, examining the impact of modulating this gene in two experimental models for PD:α-synuclein and rotenone toxicity. In both systems, PGC-1α was able to suppress toxicity"
Thanks and BDNF ?
"Brain-Derived Neurotrophic Factor". Don't ask me what it actually IS, but I know what it's supposed to do - it encourages neuron protective and re-growth. So we PWP could do with more of it! Exercise is supposed to produce more of it, and there's various clinical trials (such as Cogane) looking at ways of increasing BDNF (or it's close cousin GDNF) in PWP.
Mmj thanks for your posting, I'm not very scientific, so am trying to understand all this, have joined neurotalk now. Do you follow any of the suggestions? I have been fasting one day a week for about 8 weeks and have started taking coconut oil!
personally speakng, i am finding it increasngly difficult to keep track of the myriad of recent developments. It would be handy if research could provide a regular ovevriew - particularly of how the pieces fit together
I'm not on neurotalk myself, but I read it a lot - there's some regular posters there who are very informed and into the science and research of PD.