Accutane; P53/foxo1/foxo3 the key?

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#1


From various research, it seems concluded that Accutane strongly induces the p53 enzyme. This causes a cascade effect which then induces foxo1/foxo3, this then causes a significant increase in aptosis/cell death and also the downregulation of igf1/androgens/androgen receptors. We know accutane induces aptosis due to the up regulation of foxo1/p53/foxo3, all anti cancer targets. We also know that said targets result in heavy anti androgenic affects, igf1 downregulation, dht downregulation, 5ar downregulation, androgen receptor downregulatiom etc. This could (partly) easily explain the hormonal/endocrine issues that accutane causes. Now, to the other point, aptosis and cell death. Accutanes indiscriminat aptoptic properties target multiple cells. Cells in te hippocampus/brain, cells in the gi tract, mucosa cells, intestinal cellsā€¦etc. Increased aptosis in all of these areas could come with multiple issues and side effects, depending on the location of said cells. What do you guys think? Think this could be a major factor in accutanes mechanism of action, in regards to multiple debilitating side effects.

Also, suppression of p53 helps immensely with chemo sides. As you would imagine. https://www.ncbi.nlm.nih.gov/m/pubmed/10702639/

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#2

Donā€™t confuse short term effects with long-term effects.

#3

Donā€™t confuse short term upregulation with permanent upregulation. These Gene/enzymes could easily still be upregulated in PAS victims, hence why the suppression of acne is also permanent/semi permanent.

#4

Iā€™m glad this information is here. But, weā€™ve had posts with all kinds of alarmist tone worst case scenario speculations of permanence of condition for 10 years. We already know that Accutane is an anti-androgen.

Now how about we advance to Phase 2, of actually DOING SOMETHING instead of sitting and crying? Have you gone to Accutane communities and sexual dysfunction communities with this information and told them that we have a survey that desperately needs more Accutane participants? That would actually be doing something. If all we do is sit here wringing our hands and complaining about drug companies, then yeah, weā€™re fucked.

If we get more Accutane participants in the survey then we can get a cure and not have to sit here crying for the next 50 years. If we donā€™t get more Accutane participants in the survey, then yeah, we are going to be sitting here fucked, crying, and complaining. There isnā€™t anyone coming to rescue us because the world somehow owes us. The reality is that WE need to rescue us and the only way right now is to get the survey filled out.

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#5

The fuck are you rambling about. What does anything you said have to do with my post? Literally posting scientific info to help us and provide a discussion. Nobodies complaining.

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#6

There are already several threads about this. Itā€™s great you are here. Could you fill out the survey? They badly need Accutane participants.

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#7

Definitely appreciate your attitude towards science, itā€™s clearly the only route out of this mess. As has been said though, the survey is essential to us conducting studies. You may not yet realise its importance, but it isnā€™t easy to convince scientists to spend their valuable time studying our condition. We need these survey results and your inclusion is vital. Please complete it man. You donā€™t have to do it in one go, it saves your progress so you can do it in stages.

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#8

Where is this survey?

#9

Are you on mobile or desktop mate?

#10

You can find the link to the survey here - PSSD and post-accutane patients: Please take our survey.

If youā€™re on mobile, then just follow these instructions - Can't fill out the survey? Please post here or be reminded until you do

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#11

What the actual fuck. Felt like I was having an aneurism during the survey. Only finished 20 percent so far. Why is everything in 4 week intervals? (before after drug) alot of info to be missed doing it in that format.

#12

Because the 4 week period accounts for the typical ā€œcrashā€ that most users experience. Itā€™s essential to understanding the pathology of the disease. Thanks for starting it man. As said, you can do it in stages so you donā€™t have to do it all at once. Just keep chipping away at it.

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#13

It is annoying to do, but Iā€™m sure itā€™s like that for a reason

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#14

I didnā€™t crash till months laterā€¦I felt like shit taking the drugā€¦Felt like shit when I stoppedā€¦Then after about 3 months I felt horrible and each passing month after that I felt worse and worse and my weight kept increasing for no reasonā€¦Some have speculated a slow degradation of the 5ar geneā€¦

#15

I know itā€™s trivial and probably was mentioned before, but studies clearly show disruption of AR activity and suppression of DHT action through upregulation of p53 protein by accutaneā€¦ There is strong correlation between p53 and AR

I had 80-100% EQ and libido improvement and my response to androgenic substances such as tribulus returned while I was on glycyrrhiza glabra (licorice root) for month. I am probably trying to rationalize, and there is big chance I am wrong in implying that p53 is involved in my temporary improvements, but studies show that glabridin decrease p53 expression.

Another drug I am interested in is eplerenone. It also downregulates p53 and should be more potent than licorice root. Cistanche is another supplement that seems to downregulate P53 according to studies.

There could be a massive mess downstream of p53, not only AR.
Tp53 gene mediates distinct dopaminergic neuronal damage in different dopaminergic neurotoxicant models
https://www.nrronline.org/article.asp?issn=1673-5374;year=2017;volume=12;issue=9;spage=1413;epage=1417;aulast=Lu

Another bonus for those who wonder why accutane might cause a hair loss

These data suggest that p53 is involved in the control of apoptosis in the hair follicle during physiological regression and imply that p53 antagonists may be useful for the management of hair growth disorders characterized by premature entry into catagen, such as androgenetic alopecia , alopecia areata, and telogen

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#16

As im too a PAS sufferer, this made me very interested. Can you please state if your erection girth and length came back to pre-pas measurements too? Was it as hard as pre-pas? Firm Pc muscles too? Any cure on numb orgasms, intensity?

Personally, i forgot what my baseline erections wereā€¦ Do you even remember how things suppose to feel and seem after all these years? Im just curious. I wonder if you ā€˜ā€˜knowā€™ā€™ deep inside your mind that your sexuality and prostate orgasms fixed 100% or not when you recoverā€¦

Any details, appreciated. @slick1

#17

Can someone please help me to understand these stuides? I am plainly suicidal. I have never experienced this kind of strong hopelesness beforeā€¦

Are these effects on increased FoxO1 tissue spesific?

Are we damaged the androgen signaling and IGF-1 signaling and its receptors on the whole body or just in the skin tissue and the sebocytes? Are all of these studies talk about skin or about the whole body?

Can we say these general effects are persistent on PAS patients? These effects must be temporary on normal people, but how about us?

I donā€™t know why im seeing these after all these years, but please someone help me to understand. I just talked about with my mom that im going to kill myself if HCG wonā€™t work on me.

This is so sad. It surely damaged my development if it increased my FoxO persistently due to PAS.

This explains everything. My worst fears came actually true, i live in a nightmare.

@AccutaneZombie @Dubya_B @guitarman01

#18

while I was on licorice not only EQ and size improved, but also the glans became hard like pre PAS. I am doing more research nowā€¦ Given that Foxo1 disrupts AR function as well and is interconnected with p53 , we can assume itā€™s upregulation by isotretinoin might play some role in PAS.

Hispaglabridin B, a constituent of liquorice
identified by a bioinformatics and machine
learning approach, relieves protein-energy
wasting by inhibiting forkhead box O1

This finding suggested that liquorice may block FoxO1 in the posttranscriptional phase. Interestingly, Western blots showed that liquorice extracts decreased the phosphorylation of FoxO1 at Ser253 but had little effect on that at Thr24, which should promote transcriptional activity (Figure 2F). Given that liquorice actually blocked transcriptional activity, we propose that the extract binds to the active site of FoxO1 and then inhibits its transcriptional activity and phosphorylation simultaneously

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#19

Thanks man. May i ask did PAS cleared your acne? My Acne didnā€™t change at all after PAS. So this FoxO study makes no sense? How is yours? @slick1

Anyone else, please contribute to this question.

#20

My cystic acne (which wasnā€™t horrible before accutane but still visible) cleared up but I still get clogged pores, whiteheads and blackheads at the same level as before. I only took accutane for 3 weeks so it wasnā€™t the accutane clearing my cystic acne up but probably PAS is what got rid of the cysts

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