Part:BBa_K1598008:Experience

Relief of Side-effects from Depression/Anxiety drugs:

Pregnenolone and its derivates prevent the development of tolerance, and augment recovery from benzodiazepine withdrawal anxiety and hyperactivity in mice. Benzodiazepines, such as Valium, are one of the most popular antidepressant/anti-anxiety drugs in the world! Basically, this removes the need to constantly increase the dosage, and reduces a plethora of side-effects, such as sedation, memory loss, etc., of various antidepressants through its interactions with receptors in the brain such as GABA (A), and the production of other neuro-active compounds.[1]

Schizophrenia Treatment

Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic candidate in schizophrenia. Pregnenolone is a neurosteroid with pleiotropic actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further, pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABA(A) receptor responses. In addition, pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. There are thus multiple mechanistic possibilities for pregnenolone as a potential therapeutic agent in schizophrenia, including the amelioration of NMDA receptor hypofunction (via metabolism to pregnenolone sulfate) and the mitigation of GABA dysregulation (via metabolism to allopregnanolone). [2]

Memory, Cognition, and Neurotransmission

Neurosteroids derived from Pregnenolone modulate several neurotransmitter systems such as gamma-aminobutyric acid type A (GABA(A)), N-methyl-D-aspartate (NMDA) and acetylcholine receptors. As physiologic consequences, they are involved in neuronal plasticity, learning and memory processes, aggression and epilepsy, and they modulate the responses to stress, anxiety and depression. There is evidence for a common mechanism of action between neurosteroids and sigma1-receptor ligands and focus on the potential therapeutic interests of such interaction in the physiopathology of learning and memory impairments, stress, depression and neuroprotection. [3]

Steroid Biosynthesis

Pregnenolone is the precursor to all steroids, and the conversion of cholesterol into Pregnenolone is the rate limiting step of the biosynthesis of all steroids (http://www.sciencedirect.com/science/article/pii/S0143416006000856). Hence, this biobrick unlocks steroidogenesis, and paves the way for a innumerable applications in the fields of hormone replacement, fitness, birth control, immunorepression, etc.

(Source:https://en.wikiversity.org/wiki/Wikiversity_Journal_of_Medicine/Diagram_of_the_pathways_of_human_steroidogenesis)

User Reviews

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References

• [1] Reddy DS and Kulkami SK Neurosteroid coadministration prevents development of tolerance and augments recovery from benzodiazepine withdrawal anxiety and hyperactivity in mice. in Methods Find Exp Clin Pharmacol. 1997 Jul-Aug;19(6):395-405
• [2] Marx CE et al. Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence. in Neuroscience. 2011 Sep 15;191:78-90. doi: 10.1016/j.neuroscience.2011.06.076. Epub 2011 Jul 1.
• [3] Maurice T et al. Neuroactive neurosteroids as endogenous effectors for the sigma1 (sigma1) receptor: pharmacological evidence and therapeutic opportunities. in Jpn J Pharmacol. 1999 Oct;81(2):125-55.
• [4] Desislava S. Makeeva Functional reconstruction of bovine P450scc steroidogenic system in Escherichia coli in American Journal of Molecular Biology, 2013, 3, 173-182