Smith-Magenis Syndrome: Molecular Basis of a Genetic-Driven Melatonin Circadian Secretion Disorder

Smith-Magenis syndrome (SMS), linked to Retinoic Acid Induced (RAI1) haploinsufficiency, is a unique model of the inversion of circadian melatonin secretion. In this regard, this model is a formidable approach to better understand circadian melatonin secretion cycle disorders and the role of the RAI1 gene in this cycle. Sleep-wake cycle disorders in SMS include sleep maintenance disorders with a phase advance and intense sleepiness around noon. These disorders have been linked to a general disturbance of sleep-wake rhythm and coexist with inverted secretion of melatonin. The exact mechanism underlying the inversion of circadian melatonin secretion in SMS has rarely been discussed. We suggest three hypotheses that could account for the inversion of circadian melatonin secretion and discuss them. First, inversion of the circadian melatonin secretion rhythm could be linked to alterations in light signal transduction. Second, this inversion could imply global misalignment of the circadian system. Third, the inversion is not linked to a global circadian clock shift but rather to a specific impairment in the melatonin secretion pathway between the suprachiasmatic nuclei (SCN) and pinealocytes. The development of diurnal SMS animal models that produce melatonin appears to be an indispensable step to further understand the molecular basis of the circadian melatonin secretion rhythm.

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Photic Entrainment of the Circadian System

International Journal of Molecular Sciences ◽

10.3390/ijms23020729 ◽

2022 ◽

Vol 23 (2) ◽

pp. 729

Author(s):

Anna Ashton ◽

Russell G. Foster ◽

Aarti Jagannath

Keyword(s):

Circadian Clock ◽

Molecular Basis ◽

Feedback Loop ◽

Molecular Mechanisms ◽

External World ◽

Circadian System ◽

Suprachiasmatic Nuclei ◽

Photic Entrainment ◽

External Time ◽

Daily Changes

Circadian rhythms are essential for the survival of all organisms, enabling them to predict daily changes in the environment and time their behaviour appropriately. The molecular basis of such rhythms is the circadian clock, a self-sustaining molecular oscillator comprising a transcriptional–translational feedback loop. This must be continually readjusted to remain in alignment with the external world through a process termed entrainment, in which the phase of the master circadian clock in the suprachiasmatic nuclei (SCN) is adjusted in response to external time cues. In mammals, the primary time cue, or “zeitgeber”, is light, which inputs directly to the SCN where it is integrated with additional non-photic zeitgebers. The molecular mechanisms underlying photic entrainment are complex, comprising a number of regulatory factors. This review will outline the photoreception pathways mediating photic entrainment, and our current understanding of the molecular pathways that drive it in the SCN.

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Role of the suprachiasmatic nuclei in the circadian system of the house sparrow, Passer domesticus

Journal of Neuroscience ◽

10.1523/jneurosci.02-06-00815.1982 ◽

1982 ◽

Vol 2 (6) ◽

pp. 815-828 ◽

Cited By ~ 101

Author(s):

JS Takahashi ◽

M Menaker

Keyword(s):

House Sparrow ◽

Passer Domesticus ◽

Circadian System ◽

Suprachiasmatic Nuclei

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Synchronization of Fibroblasts Ex Vivo in Psychopharmacology

Pharmacopsychiatry ◽

10.1055/a-1151-4947 ◽

2020 ◽

Author(s):

Frank Faltraco ◽

Adriana Uzoni ◽

Liliia Shevchuk ◽

Johannes Thome ◽

Denise Palm

Keyword(s):

Current Knowledge ◽

Ex Vivo ◽

Circadian System ◽

Suprachiasmatic Nuclei ◽

Circadian Gene ◽

Peripheral Oscillators ◽

Rat Fibroblasts ◽

Inner Clock ◽

Central Oscillator

AbstractThe central oscillator for the inner clock is the suprachiasmatic nuclei of the hypothalamus. Furthermore, many peripheral oscillators are present in tissues such as skin. Human derived fibroblasts provide an advantageous model to study circadian rhythmicity as well as the influence of pharmacological drugs on circadian gene expression. Importantly, the synchronization of the circadian system of fibroblasts can be done by different methods. The review presents an overview of the current knowledge of different synchronization methods mostly used in mice or rat fibroblasts. Furthermore, the review sums up and discusses the role of norepinephrine as a possible synchronizer agent.

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The role of the Na+/H+ exchange system in cardiac cells in relation to the control of the internal Na+ concentration. A molecular basis for the antagonistic effect of ouabain and amiloride on the heart.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)47236-x ◽

1984 ◽

Vol 259 (14) ◽

pp. 8880-8885 ◽

Cited By ~ 3

Author(s):

C Frelin ◽

P Vigne ◽

M Lazdunski

Keyword(s):

Molecular Basis ◽

Antagonistic Effect ◽

Cardiac Cells ◽

Exchange System

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Does the Interaction between Local and Systemic Inflammation Provide a Link from Psychology and Lifestyle to Tissue Health in Musculoskeletal Conditions?

International Journal of Molecular Sciences ◽

10.3390/ijms22147299 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7299

Author(s):

David M. Klyne ◽

Mary F. Barbe ◽

Greg James ◽

Paul W. Hodges

Keyword(s):

Connective Tissue ◽

Systemic Inflammation ◽

Molecular Basis ◽

Tissue Level ◽

Lifestyle Factors ◽

Local Inflammation ◽

Musculoskeletal Conditions ◽

Tissue Biology ◽

Mind And Body

Musculoskeletal conditions are known to involve biological, psychological, social and, often, lifestyle elements. However, these domains are generally considered in isolation from each other. This siloed approach is unlikely to be adequate to understand the complexity of these conditions and likely explains a major component of the disappointing effects of treatment. This paper presents a hypothesis that aims to provide a foundation to understand the interaction and integration between these domains. We propose a hypothesis that provides a plausible link between psychology and lifestyle factors with tissue level effects (such as connective tissue dysregulation/accumulation) in musculoskeletal conditions that is founded on understanding the molecular basis for interaction between systemic and local inflammation. The hypothesis provides plausible and testable links between mind and body, for which empirical evidence can be found for many aspects. We present this hypothesis from the perspective of connective tissue biology and pathology (fibrosis), the role of inflammation locally (tissue level), and how this inflammation is shaped by systemic inflammation through bidirectional pathways, and various psychological and lifestyle factors via their influence on systemic inflammation. This hypothesis provides a foundation for new consideration of the development and refinement of personalized multidimensional treatments for individuals with musculoskeletal conditions.

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From Capsids to Complexes: Expanding the Role of TRIM5α in the Restriction of Divergent RNA Viruses and Elements

Viruses ◽

10.3390/v13030446 ◽

2021 ◽

Vol 13 (3) ◽

pp. 446

Author(s):

Kevin M. Rose ◽

Stephanie J. Spada ◽

Rebecca Broeckel ◽

Kristin L. McNally ◽

Vanessa M. Hirsch ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Molecular Basis ◽

Human Population ◽

Rna Viruses ◽

Arms Race ◽

Innate Immune ◽

Immunodeficiency Virus ◽

Underlying Mechanisms ◽

Hiv 1

An evolutionary arms race has been ongoing between retroviruses and their primate hosts for millions of years. Within the last century, a zoonotic transmission introduced the Human Immunodeficiency Virus (HIV-1), a retrovirus, to the human population that has claimed the lives of millions of individuals and is still infecting over a million people every year. To counteract retroviruses such as this, primates including humans have evolved an innate immune sensor for the retroviral capsid lattice known as TRIM5α. Although the molecular basis for its ability to restrict retroviruses is debated, it is currently accepted that TRIM5α forms higher-order assemblies around the incoming retroviral capsid that are not only disruptive for the virus lifecycle, but also trigger the activation of an antiviral state. More recently, it was discovered that TRIM5α restriction is broader than previously thought because it restricts not only the human retroelement LINE-1, but also the tick-borne flaviviruses, an emergent group of RNA viruses that have vastly different strategies for replication compared to retroviruses. This review focuses on the underlying mechanisms of TRIM5α-mediated restriction of retroelements and flaviviruses and how they differ from the more widely known ability of TRIM5α to restrict retroviruses.

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