MicroRNA in glutamate receptor-dependent neurological diseases

2017 ◽  
Vol 131 (14) ◽  
pp. 1591-1604 ◽  
Author(s):  
Walid A. Alsharafi ◽  
Zhaohui Luo ◽  
Xiaoyan Long ◽  
Yuanyuan Xie ◽  
Bo Xiao
Keyword(s):  
Glutamate Receptor ◽  
Therapeutic Target ◽  
Recent Literature ◽  
Neurological Diseases ◽  
Present Review ◽  
Regulatory Mechanisms ◽  
Promising Therapeutic Target ◽  
Wide Range

Glutamate-mediated excitotoxicity is the major neuropathological process contributing to numerous neurological diseases. Recently, emerging evidence indicates that microRNAs (miRNAs) play essential roles in the pathophysiology of a wide range of neurological diseases. Notably, there have been significant developments in understanding the biogenesis of miRNAs, their regulatory mechanisms, and their potential as effective biomarkers and therapies. In the present review, we summarize the recent literature that highlights the versatile roles played by miRNAs in glutamate receptor (GluR)-dependent neurological diseases. Based on the reported studies to date, modulation of miRNAs could emerge as a promising therapeutic target for a variety of neurological diseases that were discussed in this review.

scholarly journals CHIP as a therapeutic target for neurological diseases

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Shuo Zhang ◽  
Zheng-wei Hu ◽  
Cheng-yuan Mao ◽  
Chang-he Shi ◽  
Yu-ming Xu
Keyword(s):  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Critical Role ◽  
Interacting Protein ◽  
Ubiquitin E3 Ligase ◽  
Promising Therapeutic Target ◽  
Wide Range ◽  
Range Of Functions ◽  
The Central Nervous System

Abstract Carboxy-terminus of Hsc70-interacting protein (CHIP) functions both as a molecular co-chaperone and ubiquitin E3 ligase playing a critical role in modulating the degradation of numerous chaperone-bound proteins. To date, it has been implicated in the regulation of numerous biological functions, including misfolded-protein refolding, autophagy, immunity, and necroptosis. Moreover, the ubiquitous expression of CHIP in the central nervous system suggests that it may be implicated in a wide range of functions in neurological diseases. Several recent studies of our laboratory and other groups have highlighted the beneficial role of CHIP in the pathogenesis of several neurological diseases. The objective of this review is to discuss the possible molecular mechanisms that contribute to the pathogenesis of neurological diseases in which CHIP has a pivotal role, such as stroke, intracerebral hemorrhage, Alzheimer’s disease, Parkinson’s disease, and polyglutamine diseases; furthermore, CHIP mutations could also cause neurodegenerative diseases. Based on the available literature, CHIP overexpression could serve as a promising therapeutic target for several neurological diseases.

MMP-12, a Promising Therapeutic Target for Neurological Diseases

2017 ◽  
Vol 55 (2) ◽  
pp. 1405-1409 ◽  
Author(s):  
Bharath Chelluboina ◽  
Koteswara Rao Nalamolu ◽  
Jeffrey D. Klopfenstein ◽  
David M. Pinson ◽  
David Z. Wang ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Neurological Diseases ◽  
Promising Therapeutic Target

scholarly journals Targeting RIPK1 for the treatment of human diseases

2019 ◽  
Vol 116 (20) ◽  
pp. 9714-9722 ◽  
Author(s):  
Alexei Degterev ◽  
Dimitry Ofengeim ◽  
Junying Yuan
Keyword(s):  
Cell Death ◽  
Brain Injuries ◽  
Inflammatory Diseases ◽  
Neurological Diseases ◽  
Human Diseases ◽  
Necrotic Cell ◽  
Promising Therapeutic Target ◽  
Wide Range ◽  
Autoimmune And Inflammatory Diseases ◽  
Central Nervous Systems

RIPK1 kinase has emerged as a promising therapeutic target for the treatment of a wide range of human neurodegenerative, autoimmune, and inflammatory diseases. This was supported by extensive studies which demonstrated that RIPK1 is a key mediator of apoptotic and necrotic cell death as well as inflammatory pathways. Furthermore, human genetic evidence has linked the dysregulation of RIPK1 to the pathogenesis of ALS as well as other inflammatory and neurodegenerative diseases. Importantly, unique allosteric small-molecule inhibitors of RIPK1 that offer high selectivity have been developed. These molecules can penetrate the blood–brain barrier, thus offering the possibility to target neuroinflammation and cell death which drive various neurologic conditions including Alzheimer’s disease, ALS, and multiple sclerosis as well as acute neurological diseases such as stroke and traumatic brain injuries. We discuss the current understanding of RIPK1 regulatory mechanisms and emerging evidence for the pathological roles of RIPK1 in human diseases, especially in the context of the central nervous systems.

scholarly journals Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Bangrong Cai ◽  
Ying Zhang ◽  
Zengtao Wang ◽  
Dujuan Xu ◽  
Yongyan Jia ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Therapeutic Agents ◽  
Present Review ◽  
Recent Advances ◽  
Wide Range ◽  
The Central Nervous System

Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as Dioscorea rhizome, Dioscorea villosa, Trigonella foenum-graecum, Smilax China, and Rhizoma polgonati. DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. Due to its wide range of pharmacological activities and medicinal properties, it has been used in the treatment of cancers, hyperlipidemia, inflammation, and infections. Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. Its therapeutic mechanisms are based on the mediation of different signaling pathways, and targeting these pathways might lead to the development of effective therapeutic agents for neurological diseases. The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson’s disease, Alzheimer’s disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG. In the present review, databases of PubMed, Web of Science, and Scopus were used for studies of DG and its derivatives in the treatment of central nervous system diseases published in English until December 10, 2019. Three independent researchers examined articles for eligibility. A total of 150 articles were screened from the above scientific literature databases. Finally, a total of 46 articles were extracted and included in this review. Keywords related to glioma, ischemia, memory, aging, cognitive impairment, Alzheimer, Parkinson, and neurodegenerative disorders were searched in the databases based on DG and its derivatives.

Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1 G93G Mice Predates Disease Onset and is a Promising Therapeutic Target

2019 ◽  
Author(s):  
Silvia Scaricamazza ◽  
Illari Salvatori ◽  
Giacomo Giacovazzo ◽  
Jean Philippe Loeffler ◽  
Frederique Renè ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Therapeutic Target ◽  
Disease Onset ◽  
Metabolic Reprogramming ◽  
Promising Therapeutic Target

A Brief Review on the Development of Novel Potentially Active Azetidin-2-ones Against Cancer

2020 ◽  
Vol 24 (5) ◽  
pp. 473-486 ◽  
Author(s):  
Ligia S. da Silveira Pinto ◽  
Thatyana R. Alves Vasconcelos ◽  
Claudia Regina B. Gomes ◽  
Marcus Vinícius N. de Souza
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Present Review ◽  
Pharmacological Properties ◽  
Important Group ◽  
Wide Range ◽  
Anti Inflammatory

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.

Enzymes as a Reservoir of Host Defence Peptides

2020 ◽  
Vol 20 (14) ◽  
pp. 1310-1323
Author(s):  
Andrea Bosso ◽  
Antimo Di Maro ◽  
Valeria Cafaro ◽  
Alberto Di Donato ◽  
Eugenio Notomista ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Biological Activity ◽  
Internal Structure ◽  
Catalytic Properties ◽  
Cellular Responses ◽  
Host Defence ◽  
Present Review ◽  
Active Peptides ◽  
Wide Range

Host defence peptides (HDPs) are powerful modulators of cellular responses to various types of insults caused by pathogen agents. To date, a wide range of HDPs, from species of different kingdoms including bacteria, plant and animal with extreme diversity in structure and biological activity, have been described. Apart from a limited number of peptides ribosomally synthesized, a large number of promising and multifunctional HDPs have been identified within protein precursors, with properties not necessarily related to innate immunity, consolidating the fascinating hypothesis that proteins have a second or even multiple biological mission in the form of one or more bio-active peptides. Among these precursors, enzymes constitute certainly an interesting group, because most of them are mainly globular and characterized by a fine specific internal structure closely related to their catalytic properties and also because they are yet little considered as potential HDP releasing proteins. In this regard, the main aim of the present review is to describe a panel of HDPs, identified in all canonical classes of enzymes, and to provide a detailed description on hydrolases and their corresponding HDPs, as there seems to exist a striking link between these structurally sophisticated catalysts and their high content in cationic and amphipathic cryptic peptides.

scholarly journals What If the ‘Anthropocene’ Is Not Formalized as a New Geological Series/Epoch?

Quaternary ◽  
2018 ◽  
Vol 1 (3) ◽  
pp. 24 ◽  
Author(s):  
Valentí Rull
Keyword(s):  
Present State ◽  
Executive Committee ◽  
Working Group ◽  
Recent Literature ◽  
Special Issue ◽  
Environmental Sciences ◽  
International Union ◽  
Quaternary Stratigraphy ◽  
Wide Range ◽  
Geological Sciences

In the coming years, the Anthropocene Working Group (AWG) will submit its proposal on the ‘Anthropocene’ to the Subcommission of Quaternary Stratigraphy (SQS) and the International Commission on Stratigraphy (ICS) for approval. If approved, the proposal will be sent to the Executive Committee of the International Union of Geological Sciences (IUGS) for ratification. If the proposal is approved and ratified, then the ‘Anthropocene’ will be formalized. Currently, the ‘Anthropocene’ is a broadly used term and concept in a wide range of scientific and non-scientific situations, and, for many, the official acceptance of this term is only a matter of time. However, the AWG proposal, in its present state, seems to not fully meet the requirements for a new chronostratigraphic unit. This essay asks what could happen if the current ‘Anthropocene’ proposal is not formalized by the ICS/IUGS. The possible stratigraphic alternatives are evaluated on the basis of the more recent literature and the personal opinions of distinguished AWG, SQS, and ICS members. The eventual impact on environmental sciences and on non-scientific sectors, where the ‘Anthropocene’ seems already firmly rooted and de facto accepted as a new geological epoch, are also discussed. This essay is intended as the editorial introduction to a Quaternary special issue on the topic.

scholarly journals Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732110227
Author(s):  
Friederike Held ◽  
Sudhakar Reddy Kalluri ◽  
Achim Berthele ◽  
Ana-Katharina Klein ◽  
Markus Reindl ◽  
...  
Keyword(s):  
Time Course ◽  
Neurological Diseases ◽  
External Validation ◽  
Diagnostic Value ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Large Cohort ◽  
Wide Range ◽  
Neurological Patients ◽  
A Cell ◽  
Nosological Entity

Background Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab. Objective To investigate the seroprevalence of MOG-Ab under consideration of demographics, disease entities and time course in a large cohort of unselected neurological patients. Methods Blood samples of 2.107 consecutive adult neurologic patients admitted to our department between 2016-2017 were tested for MOG-Ab using a cell-based assay. MOG-Ab persistence was analyzed in follow-up samples. External validation was performed in two independent laboratories. Results We found MOG-Ab in 25 of 2.107 (1.2%) patients. High antibody ratios were mostly associated with NMOSD and MOG-AD phenotype (5/25). Low ratios occurred in a wide range of neurological diseases, predominantly in other demyelinating CNS diseases (5/25) and stroke (6/25). MOG-Ab persistence over time was not confined to NMOSD and MOG-AD phenotype. Conclusion The present study demonstrates the occurrence of MOG-Ab in a wide range of neurological diseases. Only high MOG-Ab ratios were associated with a defined clinical phenotype, but low MOG-Ab ratios were not. The diagnostic value of low MOG-Ab is thus highly limited.

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