scholarly journals The emerging role of the KCTD proteins in cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Annapaola Angrisani ◽  
Annamaria Di Fiore ◽  
Enrico De Smaele ◽  
Marta Moretti
Keyword(s):  
Neurological Disorders ◽  
Current Knowledge ◽  
Family Members ◽  
Protein Targets ◽  
Cancer Hallmarks ◽  
Published Evidence ◽  
Oncogenic Pathways ◽  
Tetramerization Domain ◽  
Human Family

AbstractThe human family of Potassium (K+) Channel Tetramerization Domain (KCTD) proteins counts 25 members, and a significant number of them are still only partially characterized. While some of the KCTDs have been linked to neurological disorders or obesity, a growing tally of KCTDs are being associated with cancer hallmarks or involved in the modulation of specific oncogenic pathways. Indeed, the potential relevance of the variegate KCTD family in cancer warrants an updated picture of the current knowledge and highlights the need for further research on KCTD members as either putative therapeutic targets, or diagnostic/prognostic markers. Homology between family members, capability to participate in ubiquitination and degradation of different protein targets, ability to heterodimerize between members, role played in the main signalling pathways involved in development and cancer, are all factors that need to be considered in the search for new key players in tumorigenesis. In this review we summarize the recent published evidence on KCTD members’ involvement in cancer. Furthermore, by integrating this information with data extrapolated from public databases that suggest new potential associations with cancers, we hypothesize that the number of KCTD family members involved in tumorigenesis (either as positive or negative modulator) may be bigger than so far demonstrated.

scholarly journals Current Knowledge of Endolysosomal and Autophagy Defects in Hereditary Spastic Paraplegia

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1678
Author(s):  
Liriopé Toupenet Marchesi ◽  
Marion Leblanc ◽  
Giovanni Stevanin
Keyword(s):  
Nervous System ◽  
Motor Neurons ◽  
Neurological Disorders ◽  
Hereditary Spastic Paraplegia ◽  
Current Knowledge ◽  
Spastic Paraplegia ◽  
Functional Convergence ◽  
The Common ◽  
Hsp Genes

Hereditary spastic paraplegia (HSP) refers to a group of neurological disorders involving the degeneration of motor neurons. Due to their clinical and genetic heterogeneity, finding common effective therapeutics is difficult. Therefore, a better understanding of the common pathological mechanisms is necessary. The role of several HSP genes/proteins is linked to the endolysosomal and autophagic pathways, suggesting a functional convergence. Furthermore, impairment of these pathways is particularly interesting since it has been linked to other neurodegenerative diseases, which would suggest that the nervous system is particularly sensitive to the disruption of the endolysosomal and autophagic systems. In this review, we will summarize the involvement of HSP proteins in the endolysosomal and autophagic pathways in order to clarify their functioning and decipher some of the pathological mechanisms leading to HSP.

scholarly journals Dangerous Duplicity: The Dual Functions of Casein Kinase 1in Parasite Biology and Host Subversion

2021 ◽  
Vol 11 ◽  
Author(s):  
Najma Rachidi ◽  
Uwe Knippschild ◽  
Gerald F. Späth
Keyword(s):  
Current Knowledge ◽  
Family Members ◽  
Casein Kinase ◽  
Biological Processes ◽  
Casein Kinase 1 ◽  
Parasite Survival ◽  
Host Pathogen ◽  
Parasite Biology ◽  
Antimicrobial Interventions

Casein Kinase 1 (CK1) family members are serine/threonine protein kinases that are involved in many biological processes and highly conserved in eukaryotes from protozoan to humans. Even though pathogens exploit host CK1 signaling pathways to survive, the role of CK1 in infectious diseases and host/pathogen interaction is less well characterized compared to other diseases, such as cancer or neurodegenerative diseases. Here we present the current knowledge on CK1 in protozoan parasites highlighting their essential role for parasite survival and their importance for host-pathogen interactions. We also discuss how the dual requirement of CK1 family members for parasite biological processes and host subversion could be exploited to identify novel antimicrobial interventions.

scholarly journals BDNF signaling during the lifetime of dendritic spines

2020 ◽  
Vol 382 (1) ◽  
pp. 185-199 ◽  
Author(s):  
Marta Zagrebelsky ◽  
Charlotte Tacke ◽  
Martin Korte
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Conclusive Evidence ◽  
Excitatory Synapses ◽  
Neuronal Homeostasis ◽  
Bdnf Signaling ◽  
Spine Number

Abstract Dendritic spines are tiny membrane specialization forming the postsynaptic part of most excitatory synapses. They have been suggested to play a crucial role in regulating synaptic transmission during development and in adult learning processes. Changes in their number, size, and shape are correlated with processes of structural synaptic plasticity and learning and memory and also with neurodegenerative diseases, when spines are lost. Thus, their alterations can correlate with neuronal homeostasis, but also with dysfunction in several neurological disorders characterized by cognitive impairment. Therefore, it is important to understand how different stages in the life of a dendritic spine, including formation, maturation, and plasticity, are strictly regulated. In this context, brain-derived neurotrophic factor (BDNF), belonging to the NGF-neurotrophin family, is among the most intensively investigated molecule. This review would like to report the current knowledge regarding the role of BDNF in regulating dendritic spine number, structure, and plasticity concentrating especially on its signaling via its two often functionally antagonistic receptors, TrkB and p75NTR. In addition, we point out a series of open points in which, while the role of BDNF signaling is extremely likely conclusive, evidence is still missing.

scholarly journals Cortactin signalling and dynamic actin networks

2004 ◽  
Vol 382 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Roger J. DALY
Keyword(s):  
Tyrosine Kinase ◽  
Actin Cytoskeleton ◽  
Current Knowledge ◽  
Actin Binding ◽  
Related Protein ◽  
Protein Targets ◽  
Actin Networks ◽  
Multiple Protein ◽  
Initial Characterization

Cortactin was first identified over a decade ago, and its initial characterization as both an F-actin binding protein and v-Src substrate suggested that it was likely to be a key regulator of actin rearrangements in response to tyrosine kinase signalling. The recent discovery that cortactin binds and activates the actin related protein (Arp)2/3 complex, and thus regulates the formation of branched actin networks, together with the identification of multiple protein targets of the cortactin SH3 domain, have revealed diverse cellular roles for this protein. This article reviews current knowledge regarding the role of cortactin in signalling to the actin cytoskeleton in the context of these developments.

The Diverse Roles of the IL-36 Family in Gastrointestinal Inflammation and Resolution

2020 ◽  
Author(s):  
Gemma Leon ◽  
Seamus Hussey ◽  
Patrick T Walsh
Keyword(s):  
Inflammatory Bowel Disease ◽  
Intestinal Mucosa ◽  
Significant Influence ◽  
Clinical Setting ◽  
Bowel Disease ◽  
Current Knowledge ◽  
Family Members ◽  
Inflammatory Bowel ◽  
Gastrointestinal Inflammation

Abstract The interleukin (IL)-36 family is a member of the IL-1 superfamily of cytokines and, in common with other IL-1 family members, has been shown to exhibit pleiotropic effects in homeostasis and inflammation. Although the important role these cytokines play in the skin has been widely reported, recent evidence suggests that IL-36 family members are expressed and can also exert significant influence at the intestinal mucosa. In this review, we summarize current knowledge surrounding the role of the IL-36 in the intestines. In particular, we examine its likely dichotomous role as a mediator of both inflammation and resolution, highlighting its overlapping roles in innate and adaptive inflammation at the mucosa and its contribution to pathophysiology of inflammatory bowel disease. We also summarize the complexities of targeting this cytokine family in a clinical setting.

scholarly journals The role of neuropeptide somatostatin in the brain and its application in treating neurological disorders

2021 ◽  
Author(s):  
You-Hyang Song ◽  
Jiwon Yoon ◽  
Seung-Hee Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Cortical Circuits ◽  
Protein Marker ◽  
And Function ◽  
Novel Drug ◽  
The Brain

AbstractSomatostatin (SST) is a well-known neuropeptide that is expressed throughout the brain. In the cortex, SST is expressed in a subset of GABAergic neurons and is known as a protein marker of inhibitory interneurons. Recent studies have identified the key functions of SST in modulating cortical circuits in the brain and cognitive function. Furthermore, reduced expression of SST is a hallmark of various neurological disorders, including Alzheimer’s disease and depression. In this review, we summarize the current knowledge on SST expression and function in the brain. In particular, we describe the physiological roles of SST-positive interneurons in the cortex. We further describe the causal relationship between pathophysiological changes in SST function and various neurological disorders, such as Alzheimer’s disease. Finally, we discuss potential treatments and possibility of novel drug developments for neurological disorders based on the current knowledge on the function of SST and SST analogs in the brain derived from experimental and clinical studies.

scholarly journals The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1813
Author(s):  
Barbara Kosmowska ◽  
Jadwiga Wardas
Keyword(s):  
Animal Models ◽  
Essential Tremor ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Disease Symptoms ◽  
Motor Thalamus ◽  
New Strategies ◽  
Deep Brain

Essential tremor (ET) is one of the most common neurological disorders that often affects people in the prime of their lives, leading to a significant reduction in their quality of life, gradually making them unable to independently perform the simplest activities. Here we show that current ET pharmacotherapy often does not sufficiently alleviate disease symptoms and is completely ineffective in more than 30% of patients. At present, deep brain stimulation of the motor thalamus is the most effective ET treatment. However, like any brain surgery, it can cause many undesirable side effects; thus, it is only performed in patients with an advanced disease who are not responsive to drugs. Therefore, it seems extremely important to look for new strategies for treating ET. The purpose of this review is to summarize the current knowledge on the pathomechanism of ET based on studies in animal models of the disease, as well as to present and discuss the results of research available to date on various substances affecting dopamine (mainly D3) or adenosine A1 receptors, which, due to their ability to modulate harmaline-induced tremor, may provide the basis for the development of new potential therapies for ET in the future.

scholarly journals Myosin XVI in the Nervous System

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1903
Author(s):  
Elek Telek ◽  
András Kengyel ◽  
Beáta Bugyi
Keyword(s):  
Nervous System ◽  
Neurological Disorders ◽  
Current Knowledge ◽  
Structural Features ◽  
Neural Cells ◽  
Cellular Functions ◽  
Cytoskeleton Reorganization ◽  
Neural Tissues ◽  
Cell Signaling Pathways

The myosin family is a large inventory of actin-associated motor proteins that participate in a diverse array of cellular functions. Several myosin classes are expressed in neural cells and play important roles in neural functioning. A recently discovered member of the myosin superfamily, the vertebrate-specific myosin XVI (Myo16) class is expressed predominantly in neural tissues and appears to be involved in the development and proper functioning of the nervous system. Accordingly, the alterations of MYO16 has been linked to neurological disorders. Although the role of Myo16 as a generic actin-associated motor is still enigmatic, the N-, and C-terminal extensions that flank the motor domain seem to confer unique structural features and versatile interactions to the protein. Recent biochemical and physiological examinations portray Myo16 as a signal transduction element that integrates cell signaling pathways to actin cytoskeleton reorganization. This review discusses the current knowledge of the structure-function relation of Myo16. In light of its prevalent localization, the emphasis is laid on the neural aspects.

scholarly journals The Functions of the Mammalian Methionine Sulfoxide Reductase System and Related Diseases

Antioxidants ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 122 ◽  
Author(s):  
Beichen Jiang ◽  
Jackob Moskovitz
Keyword(s):  
Neurological Disorders ◽  
Current Knowledge ◽  
Methionine Sulfoxide ◽  
Review Article ◽  
Methionine Sulfoxide Reductase ◽  
Molecular Processes ◽  
General Role ◽  
Health And Disease ◽  
Mammalian System

This review article describes and discusses the current knowledge on the general role of the methionine sulfoxide reductase (MSR) system and the particular role of MSR type A (MSRA) in mammals. A powerful tool to investigate the contribution of MSRA to molecular processes within a mammalian system/organism is the MSRA knockout. The deficiency of MSRA in this mouse model provides hints and evidence for this enzyme function in health and disease. Accordingly, the potential involvement of MSRA in the processes leading to neurodegenerative diseases, neurological disorders, cystic fibrosis, cancer, and hearing loss will be deliberated and evaluated.

Epilepsy and vitamin D: a comprehensive review of current knowledge

2017 ◽  
Vol 28 (2) ◽  
pp. 185-201 ◽  
Author(s):  
Seyed Amir Miratashi Yazdi ◽  
Mehdi Abbasi ◽  
Seyed Masoud Miratashi Yazdi
Keyword(s):  
Vitamin D ◽  
Neurological Disorders ◽  
Potential Role ◽  
Current Knowledge ◽  
Current Evidence ◽  
Action Mechanism ◽  
Epileptic Patients ◽  
The Central Nervous System ◽  
The Impact

AbstractVitamin D has been considered as neurosteroid, and its pivotal role in neuroprotection, brain development, and immunomodulation has been noticed in studies; however, our knowledge regarding its role in neurological disorders is still developing. The potential role of vitamin D in the pathophysiology and treatment of epilepsy, as one the most prevalent neurological disorders, has received less attention in recent years. In this article, we review the possible relationship between vitamin D and epilepsy from different aspects, including the action mechanism of vitamin D in the central nervous system and ecological and epidemiological findings. We also present the outcome of studies that evaluated the level of vitamin D and the impact of administrating vitamin D in epileptic patients or animal subjects. We also review the current evidence on interactions between vitamin D and antiepileptic drugs.

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