From Urocortin reverses Parkinsonian like effects of intra-nigral lipopolysaccaride injection

2007

The current data provide further evidence for a potential neuroprotective role for UCN inmodels of PD. Given that PD is almost certainly the result of complex multifactorial events, theactions of UCN may be especially fortuitous. By combining both anti-apoptotic and anti-inflammatory properties it may be that UCN combines actions to yield an ‘anti-Parkinsonian’like effect. It is our opinion that the development of CNS permeable ligands for the UCN receptor could constitute a significant development in the therapy of PD.

http://www.pa2online.org/abstracts/V...e2abst156P.pdf

Urocortin is a peptide produced primarily in the brain. Neurons may have two different types of receptors or "switches" that a urocortin molecule can activate or "turn on". Those two receptors are imaginatively called "1" and "2".

Receptor 1 is part of the stress system and receptor 2 is part of our "appestat" or appetite control.

AmI close so far? If so- Receptor 1 is what we are most interested in. Since it is tied into the stress system, I wonder if this is where our weird stress sensitivity enters the picture in some way?

I wonder, too, if there are ways to boost the supply of "keys" (ligands?) in hopes of triggering a similar effect. Would these be substances that make us feel good? Is this involved with anti-depressant induced neurogenesis?

This helped a bit:

1: Brain Res. 1999 Nov 27;848(1-2):141-52.

A role for corticotropin releasing factor and urocortin in behavioral responses
to stressors.

Koob GF, Heinrichs SC.

Department of Neuropharmacology, CVN-7, The Scripps Research Institute, La Jolla,
CA 92037, USA. gkoob@scripps.edu

Corticotropin-releasing factor (CRF) and CRF-related neuropeptides have an
important role in the central nervous system to mediate behavioral responses to
stressors. CRF receptor antagonists are very effective in reversing
stress-induced suppression and activation in behavior. An additional CRF-like
neuropeptide, urocortin, has been identified in the brain and has a high affinity
for the CRF-2 receptor in addition to the CRF-1 receptor. Urocortin has many of
the effects of CRF but also is significantly more potent than CRF in decreasing
feeding in both meal-deprived and free-feeding rats. In mouse genetic models,
mice over-expressing CRF show anxiogenic-like responses compared to wild-type
mice, and mice lacking the CRF-1 receptor showed an anxiolytic-like behavioral
profile compared to wild-type mice. Results to date have led to the hypothesis
that CRF-1 receptors may mediate CRF-like neuropeptide effects on behavioral
responses to stressors, but CRF-2 receptors may mediate the suppression of
feeding produced by CRF-like neuropeptides. Brain sites for the behavioral
effects of CRF include the locus coeruleus (LC), paraventricular nucleus (PVN) of
the hypothalamus, the bed nucleus of the stria terminalis (BNST), and the central
nucleus of the amygdala. CRF may also be activated during acute withdrawal from
all major drugs of abuse, and recent data suggest that CRF may contribute to the
dependence and vulnerability to relapse associated with chronic administration of
drugs of abuse. These data suggest that CRF systems in the brain have a unique
role in mediating behavioral responses to diverse stressors. These systems may be
particularly important in situations were an organism must mobilize not only the
pituitary adrenal system, but also the central nervous system in response to
environmental challenge. Clearly, dysfunction in such a fundamental
brain-activating system may be the key to a variety of pathophysiological
conditions involving abnormal responses to stressors such as anxiety disorders,
affective disorders, and anorexia nervosa.


PMID: 10612706 [PubMed - indexed for MEDLINE]

1: J Pharmacol Exp Ther. 2004 Nov;311(2):427-40. Epub 2004 Aug 5.

Corticotropin-releasing factor in brain: a role in activation, arousal, and
affect regulation.

Heinrichs SC, Koob GF.

The Scripps Research Institute, Department of Neuropharmacology, CVN-7, 10550
North Torrey Pines Road, La Jolla, CA 92037, USA.

Organisms exposed to challenging stimuli that alter the status quo inside or
outside of the body are required for survival purposes to generate appropriate
coping responses that counteract departures from homeostasis. Identification of
an executive control mechanism within the brain capable of coordinating the
multitude of endocrine, physiological, and functional coping responses has high
utility for understanding the response of the organism to stressor exposure under
normal or pathological conditions. The corticotropin-releasing factor
(CRF)/urocortin family of neuropeptides and receptors constitutes an affective
regulatory system due to the integral role it plays in controlling neural
substrates of arousal, emotionality, and aversive processes. In particular,
available evidence from pharmacological intervention in multiple species and
phenotyping of mutant mice shows that CRF/urocortin systems mediate motor and
psychic activation, stimulus avoidance, and threat recognition responses to
aversive stimulus exposure. It is suggested that affective regulation is exerted
by CRF/urocortin systems within the brain based upon the sensitivity of local
brain sites to CRF/urocortin ligand administration and the appearance of
hypothalamo-pituitary-adrenocortical activation following stressor exposure.
Moreover, these same stress neuropeptides may constitute a mechanism for learning
to avoid noxious stimuli by facilitating the formation of so-called emotional
memories. A conceptual framework is provided for extrapolation of animal model
findings to humans and for viewing CRF/urocortin activation as a continuum
measure linking normal and pathological states.


PMID: 15297468 [PubMed - indexed for MEDLINE]

I have not been able to find where urocortin is usually prescribed for diabetes, nor that is has any contraindications...I did find that it used to help control weight as it makes you eat less, which could be a bad side effect if one is already on the lean side, as many here are.

I was curious about this, because I was wondering what would happen if someone who was not diabetic started taking this stuff? Would it make them diabetic, or just help their PD? (Assuming your doc would Rx it for you...). I know a lot of white rats who'd be willing to do this, depending on what else it might to do the body...

We're talking about two separate drugs here, correct?

Urocortin and Exenatide.

Exenatide is marketed as Byetta and is available now.

Is Urocortin currently marketed as a drug as well?

Is MJF working on either of these? (Paula)

Cal

6 Deaths Reported From Diabetes Drug Byetta
Cause of Death Varies, but Patients Had Developed Pancreatitis
By Kathleen Doheny


WebMD Health NewsReviewed by Louise Chang, MDAug. 27, 2008 -- Six patients taking the type 2 diabetes drug Byetta are reported to have died after developing pancreatitis. That's according to officials from Amylin Parmaceuticals and Eli Lily & Company, the companies that co-market the drug.

Last week, the FDA reported two deaths and four hospitalizations in Byetta patients who had pancreatitis. The four additional deaths -- announced Tuesday by company officials -- are not connected with the four hospitalizations announced by the FDA. Last week, the FDA also said it plans to strengthen warnings about serious pancreatitis problems linked to the drug.

http://diabetes.webmd.com/news/20080...eaths-reported

ABC news
http://abcnews.go.com/Health/Diabete...ory?id=5604366

Hi and thanks for this hopeful posting . Urocortin 1 sounds much better than anything else currently available . A good chance it can reverse g this dreadful disease, no invasive operations, amd no waiting for trials, right? It certainly is what I've been praying for. So why has the interest here waned?

Maybe because its impossible to get any info on its availability? I can't find any evidence of it being available as a drug/injection, given to diabetics . All I can see is that www dot PhoenixPeptide dot com sell this peptide to researchers.


This in itself may be a good lead, if one knew what to do with it. But I don't.

So, does anyone have any further information on the actual drug AVAILABLE to diabetics ?

If it was a drug sold in Europe I would be able to get it prescription-free from my trusted european pharmacist. Hope someone has an answer .Thanks , Pippa

I could not find it either, except for researchers, and even then, there were indications that the peptide available for research comes from bovine brain (no, thanks). I did read somewhere that we make urocortin on our skin, which is interesting, but not particularly helpful.

Also, should note that there are apparently three urocortins, urocortin, urocortin 2, and urocortin 3. All of my research indicated that only urocortin was helpful; indeed, the articles actually said urocortin 2 and 3 had no effect but plain urocortin had siginificant effect. Yes, very hopeful, but how does one get it, and will the plain urocortin cross the BBB? I did not get a clear answer to that particular question, but will continue to see if I can.

Rick, when do you think this will be available or rather allowed for PD patients to start taking?