Introduction: What they say:
A study from Department of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA; and Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA shows that “Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice.” This research paper was published, in the May 2017 issue of the journal “Nature communications” [One of the best research journals in Metabolism with an I.Fs of ], by Prof.Hochedlinger K, Ryan M. Walsh and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for anxiety and depression: Clomipramine (Brand name: Anafranil among others), the antidepressant drug, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression via down regulation of its target gene
From the Significance of the study to Public health relevance:
Given that: (1) one in three suffer from anxiety-related disorders worldwide; (2) nearly 12% of world population suffer from anxiety-related disorders in any given year; (3) 5-30% of people suffer from anxiety at some point in their lives; (4) 40 million adults in the US suffer from anxiety disorders; (5) nearly $42 billion a year spent in the US to treat anxiety disorders; (6) anxiety and depression are associated with higher rate of morbidity; (7) the percentage of people who suffer from anxiety is more from developed countries than from developing countries, while the opposite is true with depression; and (8) the global economic cost spent in the treatment of anxiety and depression occupies the significant portion of health care bill, there is an urgent need to find: (i) a way to cure long term anxiety and depression that are leading to a number of serious health complications; (ii) a way to induce resilience to anxiety and depression; (iii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug that not only alleviates, but also cures anxiety and depression.
What is known?
Mutations in PHF8, a histone demethylase, has been shown to result in cognitive defects and cleft lip/palate. However, its role in other physiological processes remains to be determined.
Prof.Hochedlinger Konrad’s research team has recently shown that knocking out PHF8/JMJD1.2 in mice results in: (1) no cognitive impairment; (2) up regulation of serotonin receptors Htr1a and Htr2; (3) normalization of Serotonin signalling; and (4) resistance to stress-induced anxiety- and depression-like behaviour, suggesting that inhibiting the expression of PHF8 may aid in the treatment of anxiety and depression.
From Research findings to Therapeutic opportunity:
This study suggests provides, for the first time, mechanistic insights into how Amitriptyline attenuates anxiety and depression.
Clomipramine, by increasing the expression of its target gene, it may decrease the expression of PHF8/JMJD1.2. Thereby, it may: (1) increase the expression of genes involved in serotonin signalling such as Htr1a and Htr2a; (2) normalize serotonin signalling; (3) promote resistance to stress-induced anxiety; and (4) heighten resistance to stress-induced depression-like behaviour. Thus, pharmacological formulations encompassing “Clomipramine or its analogues, either alone or in combination with other drugs, may be used to treat anxiety and depression; and promote resistance to depression- and anxiety-like behaviors (fig 1).
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How Clomipramine decreases PHF8 levels, increases serotonin receptors Htr1a and Htr2a levels, and promotes resistance to stress-induced anxiety and depression.
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Citation: Boominathan, L., Molecular therapy for anxiety and depression: Clomipramine (Brand name: Anafranil among others), the antidepressant drug, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression via down regulation of its target gene, 11/August/2017, 11.27 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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