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I don't know.

We have looked extensively at PPAR in our work on neurodegeneration and studied the effectiveness of medium chain triglycerides (8&10) to bypass defects in the pathways of astrocytes to neurons.

My hypothesis for Alzheimers is insulin resistance (IR) as the fundamental cause for the (6X) proliferation of astrocytes to compensate for the loss of insulin like growth factor signaling.

I believe autophagy enhancement is the result of reversing insulin resistance in Alzheimers. We do get short term gains from Caprylic Acid (C8) Beta-oxidation in astrocytes as well as Capric Acid (C10) lactate pathway shuttle to neurons. This is why some patients improve on coconut oil, however without reversing IR these gains are temporary.

I think metabolic syndrome impedes the autophagy pathway in many systems, however it may be a particular concern with hepatic function during viral infection..

A couple of our new abstracts will be submitted by March 4th (if we travel to the meeting or not is up to the virus). We have circled back to the autophagy pathway to explain iron associated neurodegeneration. So many things can perturb that pathway and we have been lucky to have miRNA studies to demonstrate it. It is like dominoes. You tip one and many processes are effected (either up or down regulated).

I'd like to share a few things we are working on that are not virus related.

For Parkinsons and PKAN, I suspect LAMP5 disfunction plays a very significant role for the iron features we see in the Globus Pallidus (GP). What causes dysfunction of LAMP5 expression takes us back to CoA synthesis as one of the dominoes. LAMP5 is a single domino that ultimately effects lysosome iron recycling. In around about way this takes us back to pantothenic acid deficiency and/or PANK disruption during the entry to the sulfur cycle (CoA pathway). It also may involve cysteine and glutathione peroxidase in another area of the cycle.

We have been puzzled as to why iron deposition is localized to the GP and wether it is an epiphenomena, result of cell survival via ferroptosis or whatever. We are still drilling down and suspect it is a defect at the beginning of the autophagy pathway localized to the GP specifically.

Check out LAMP5 in Protein Atlas: LAMP5. Look at the protein expression location and also click on Brain Atlas tab. Under the Brain Atlas tab is a very good example of mouse models unable recapitulate human disease.

It all makes you go hmmm.

Best.