Glucocorticoids in the Physiological and Transcriptional Regulation of 5-HT1A Receptor and the Pathogenesis of Depression

2020 ◽  
pp. 107385842097571
Author(s):  
Darakhshan Jabeen Haleem
Keyword(s):  
Transcriptional Regulation ◽  
Critical Role ◽  
Treatment Strategies ◽  
Therapeutic Agents ◽  
Stressful Events ◽  
Antagonist Activity ◽  
Treatment Of Depression ◽  
Prevalence Of Depression ◽  
Circulating Levels

There is growing increase in the global prevalence of depression, but treatment outcome of this highly disabling disease is not satisfactory. Many patients are not benefitted by the currently prescribed antidepressants—together with this partial remission is very common. Improving treatment strategies and developing better therapeutic agents for treating depression is therefore highly needed. Stress-related epigenetic changes play a critical role in the pathogenesis as well as treatment of depression. Stressful events activate hypothalamic-pituitary-adrenal axis to increase circulating levels of glucocorticoids (GCs), and a greater sensitivity to this fright and flight response increases risk of depression. A role of serotonin (5-hydroxytryptamine; 5-HT) in responses to stress and in the pathogenesis and treatment of depression is well established. Substantial evidence supports a critical role of 5-HT1A receptors in these effects of 5-HT. The present article targets stress-induced higher and sustained increases of GCs and mediated influences on the physiological as well transcriptional regulation of 5-HT1A receptors to evaluate their causal role in the pathogenesis of depression. It is suggested that synthetic compounds with antagonist activity for GC receptors and agonist activity for 5-HT1A receptors may prove better therapeutic agents for treating depression.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

scholarly journals The Osteoporosis/Microbiota Linkage: The Role of miRNA

2020 ◽  
Vol 21 (23) ◽  
pp. 8887 ◽  
Author(s):  
Massimo De Martinis ◽  
Lia Ginaldi ◽  
Alessandro Allegra ◽  
Maria Maddalena Sirufo ◽  
Giovanni Pioggia ◽  
...  
Keyword(s):  
Dynamic Equilibrium ◽  
Treatment Strategies ◽  
Therapeutic Agents ◽  
Osteoporosis Prevention ◽  
Regulate Gene Expression ◽  
Molecular Biotechnology ◽  
Non Coding Rnas ◽  
The Relationship ◽  
Complementary Mechanism

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

scholarly journals Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF

Cancer Cell ◽  
2004 ◽  
Vol 6 (6) ◽  
pp. 565-576 ◽  
Author(s):  
Jinyan Du ◽  
Hans R. Widlund ◽  
Martin A. Horstmann ◽  
Sridhar Ramaswamy ◽  
Ken Ross ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Critical Role ◽  
Melanoma Growth

The Low Molecular Weight Brain-derived Neurotrophic Factor Mimetics with Antidepressant-like Activity

2019 ◽  
Vol 25 (6) ◽  
pp. 729-737 ◽  
Author(s):  
Tatiana A. Gudasheva ◽  
Polina Povarnina ◽  
Alexey V. Tarasiuk ◽  
Sergey B. Seredenin
Keyword(s):  
Small Molecules ◽  
Neurotrophic Factor ◽  
Antidepressant Drugs ◽  
Brain Derived Neurotrophic Factor ◽  
Therapeutic Agents ◽  
Low Molecular Weight ◽  
Promising Therapeutic Target ◽  
Treatment Of Depression ◽  
Fast Acting

The search for new highly-effective, fast-acting antidepressant drugs is extremely relevant. Brain derived neurotrophic factor (BDNF) and signaling through its tropomyosin-related tyrosine kinase B (TrkB) receptor, represents one of the most promising therapeutic targets for treating depression. BDNF is a key regulator of neuroplasticity in the hippocampus and the prefrontal cortex, the dysfunction of which is considered to be the main pathophysiological hallmark of this disorder. BDNF itself has no favorable drug-like properties due to poor pharmacokinetics and possible adverse effects. The design of small, proteolytically stable BDNF mimetics might provide a useful approach for the development of therapeutic agents. Two small molecule BDNF mimetics with antidepressant-like activity have been reported, 7,8-dihydroxyflavone and the dimeric dipeptide mimetic of BDNF loop 4, GSB-106. The article reflects on the current literature on the role of BDNF as a promising therapeutic target in the treatment of depression and on the current advances in the development of small molecules on the base of this neurotrophin as potential antidepressants.

scholarly journals Critical role of post-transcriptional regulation for IFN-γ in tumor-infiltrating T cells

2018 ◽  
Vol 8 (2) ◽  
pp. e1532762 ◽  
Author(s):  
Fiamma Salerno ◽  
Aurelie Guislain ◽  
Julian J. Freen-Van Heeren ◽  
Benoit P. Nicolet ◽  
Howard A. Young ◽  
...  
Keyword(s):  
T Cells ◽  
Transcriptional Regulation ◽  
Critical Role ◽  
Ifn Γ ◽  
Post Transcriptional Regulation

scholarly journals Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luye Qin ◽  
Jamal B. Williams ◽  
Tao Tan ◽  
Tiaotiao Liu ◽  
Qing Cao ◽  
...  
Keyword(s):  
Risk Factor ◽  
Prefrontal Cortex ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Treatment Strategies ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Brain Diseases ◽  
Risk Genes

AbstractASH1L, a histone methyltransferase, is identified as a top-ranking risk factor for autism spectrum disorder (ASD), however, little is known about the biological mechanisms underlying the link of ASH1L haploinsufficiency to ASD. Here we show that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients. Knockdown of Ash1L in PFC of juvenile mice induces the downregulation of risk genes associated with ASD, intellectual disability (ID) and epilepsy. These downregulated genes are enriched in excitatory and inhibitory synaptic function and have decreased H3K4me3 occupancy at their promoters. Furthermore, Ash1L deficiency in PFC causes the diminished GABAergic inhibition, enhanced glutamatergic transmission, and elevated PFC pyramidal neuronal excitability, which is associated with severe seizures and early mortality. Chemogenetic inhibition of PFC pyramidal neuronal activity, combined with the administration of GABA enhancer diazepam, rescues PFC synaptic imbalance and seizures, but not autistic social deficits or anxiety-like behaviors. These results have revealed the critical role of ASH1L in regulating synaptic gene expression and seizures, which provides insights into treatment strategies for ASH1L-associated brain diseases.

scholarly journals The NMDA receptor and new possibilities in antidepressant therapy

2018 ◽  
Vol 72 ◽  
pp. 788-794
Author(s):  
Weronika Stasiuk ◽  
Monika Prendecka ◽  
Krzysztof Chara ◽  
Teresa Małecka-Massalska
Keyword(s):  
Nmda Receptor ◽  
Affective Disorders ◽  
Depressive Disorders ◽  
Treatment Strategies ◽  
Antidepressant Effect ◽  
Antidepressant Medications ◽  
Treatment Of Depression ◽  
Potential Alternative ◽  
Disorder Treatment

Due to the inadequate effectiveness of pharmacological methods currently being utilized in the treatment of depression, there is an ongoing need to find newer and safer treatment strategies. Studies undertaken to date aimed at finding more effective methods for the treatment of affective disorders have been widened to incorporate other neurotransmission systems. Experiments with compounds that modify the function of the glutamatergic system highlight a new direction in the study of affective disorder treatment methods. It has been shown that one of the key mechanisms in achieving an antidepressant effect is by weakening the function of the NMDA receptor. Pre-clinical as well as clinical trials have revealed that compounds that modulate the activity of the NMDA receptor are characterized by a significant antidepressant effect which identifies them as potential antidepressant medications. In this study an attempt was made at identifying the role of the NMDA receptor in the pathogenesis and therapy of depressive disorders as well as the influence of ligands (especially antagonist) of this receptor on the function of classical antidepressant medications. Results shown in the attached studies by numerous scientists will in the future potentially add to the development of more effective and safer therapies for patients with affective disorders as well as offering a potential alternative in the treatment of drug resistant forms of depression.

scholarly journals Critical role of IL‐1α in IL‐1β‐induced inflammatory responses: cooperation with NF‐κBp65 in transcriptional regulation

2018 ◽  
Vol 33 (2) ◽  
pp. 2526-2536 ◽  
Author(s):  
Anil K. Singh ◽  
Sabrina Fechtner ◽  
Mukesh Chourasia ◽  
Jerry Sicalo ◽  
Salahuddin Ahmed
Keyword(s):  
Transcriptional Regulation ◽  
Inflammatory Responses ◽  
Critical Role
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