Retinoic acid in the development, regeneration and maintenance of the nervous system

General Discussion
#1

Lets take a look at the literature review written by axolotl and awor,
AR deregulation as a key pathological driver of PFS?

So your trying to pin every symptom on the androgen receptor or some type of AR dysregulation.
Knowing what I know about retinoic acid, I think you could make a stronger case for retinoic acid if you wanted to try to create an explanation for PFS that was based around a single molecule.

Lets just go down the list here, this could all be Vitamin A deregulation, not androgens.
Muscle atrophy and muscular dysfunction
Skeletal and dental problems
Metabolic regulation
Digestive complaints, dysmotility, bile acid synthesis and microbiome
Immune system and wound healing
Dry Eye
Skin
Mitochondrial function
LH/T Deregulation
Cognitive dysfunction, Anhedonia and Anxiety
Memory and spatial processing
Insomnia and sleep disordered breathing
Head pressure
Sperm count, motility, and semen consistency
Libido, erectile function, and penile structural maintenance

https://www.nature.com/articles/nrn2212

Retinoic acid (RA) is involved in the induction of neural differentiation, motor neuron axon outgrowth and neural patterning during development, but there is growing evidence that RA could be used as a therapeutic molecule for the induction of axon regeneration and the treatment of neurodegeneration.

In peripheral nerves, RA stimulates the regenerative response. In this case it does not necessarily act directly on the neuron: Schwann cells and macrophages might be targets of RA.

#2

Got to wonder if esters play a role in all this, got to wonder if esters are too low now.

Some studies worry me when they say vitamin A 25000iu over 7 years made someone terribly ill.

#3

Involvement of retinoic acid signaling in goldfish optic nerve regeneration

Recently, we identified a retina-specific retinol-binding protein, purpurin, as a trigger molecule in the
early stage of goldfish optic nerve regeneration. Purpurin protein was secreted by photoreceptors to
injured ganglion cells, at 2–5 days after optic nerve injury. Purpurin bound to retinol induced neurite
outgrowth in retinal explant cultures and retinoic acid (RA) had a comparable effect on neurite
outgrowth. These results indicate that purpurin acts as a retinol transporter and facilitates conversion of
retinol to RA. Intracellularly, RA is transported into the nucleus with cellular retinoic acid-binding
protein IIb (CRABPIIb) and binds with retinoic acid receptor a (RARa) as a transcriptional regulator of
target genes. Here, we investigated the RA signaling through RA synthesis to RARa in the goldfish retina
during optic nerve regeneration by RT-PCR. Retinaldehyde dehydrogenase 2 (RALDH2; an RA synthetic
enzyme) mRNA was increased by 2.7-fold in the retina at 7–10 days and then gradually decreased until
40 days after nerve injury. In contrast, cytochrome P450 26a1 (CYP26a1; an RA degradative enzyme)
mRNA was decreased to less than half in the retina at 5–20 days and then gradually returned to the
control level by 40 days after nerve injury. CRABPIIb mRNA was increased by 1.5-fold in the retina at 10
days after axotomy, RARaa mRNA was increased by 1.8-fold in the retina at 10 days after axotomy. The
cellular changes in the RA signaling molecules after optic nerve injury were almost all located in the
ganglion cells, as evaluated by in situ hybridization. The present data described for the first time that RA
signaling through RALDH2 and CRABPIIb to RARa was serially upregulated in the ganglion cells at 7–10
days just after the purpurin induction. Therefore, we conclude that the triggering action of purpurin on
optic nerve regeneration is mediated by RA signaling pathway