Gene of the month: BECN1

2014 ◽  
Vol 67 (8) ◽  
pp. 656-660 ◽  
Author(s):  
Sumit Sahni ◽  
Angelica M Merlot ◽  
Sukriti Krishan ◽  
Patric J Jansson ◽  
Des R Richardson
Keyword(s):  
Neurological Disorders ◽  
Viral Infections ◽  
Critical Role ◽  
Beclin 1 ◽  
Biological Processes ◽  
Disease States ◽  
Binding Partners ◽  
Future Drug ◽  
Cellular Components ◽  
Important Therapeutic Target

The BECN1 gene encodes the Beclin-1 protein, which is a well-established regulator of the autophagic pathway. It is a mammalian orthologue of the ATG6 gene in yeast and was one of the first identified mammalian autophagy-associated genes. Beclin-1 interacts with a number of binding partners in the cell which can lead to either activation (eg, via PI3KC3/Vps34, Ambra 1, UV radiation resistance-associated gene) or inhibition (eg, via Bcl-2, Rubicon) of the autophagic pathway. Apart from its role as a regulator of autophagy, it is also shown to effect important biological processes in the cell such as apoptosis and embryogenesis. Beclin-1 has also been implicated to play a critical role in the pathology of a variety of disease states including cancer, neurological disorders (eg, Alzheimer's disease, Parkinson's disease) and viral infections. Thus, understanding the functions of Beclin-1 and its interactions with other cellular components will aid in its development as an important therapeutic target for future drug development.

scholarly journals Oxidative Stress and Autophagy in Cardiac Disease, Neurological Disorders, Aging and Cancer

2010 ◽  
Vol 3 (3) ◽  
pp. 168-177 ◽  
Author(s):  
Eric E. Essick ◽  
Flora Sam
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiac Disease ◽  
Neurological Disorders ◽  
Cell Stress ◽  
Nutrient Deprivation ◽  
Ros Production ◽  
Oxygen Species ◽  
Disease States ◽  
Cellular Components

Autophagy is a catalytic process of the bulk degradation of long-lived cellular components, ultimately resulting in lysosomal digestion within mature cytoplasmic compartments known as autophagolysosomes. Autophagy serves many functions in the cell, including maintaining cellular homeostasis, a means of cell survival during stress (e.g., nutrient deprivation or starvation) or conversely as a mechanism for cell death. Increased reactive oxygen species (ROS) production and the resulting oxidative cell stress that occurs in many disease states has been shown to induce autophagy. The following review focuses on the roles that autophagy plays in response to the ROS generated in several diseases.

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 Protease Inhibitors as Antiviral Agents

1998 ◽  
Vol 11 (4) ◽  
pp. 614-627 ◽  
Author(s):  
A. K. Patick ◽  
K. E. Potts
Keyword(s):  
Protease Inhibitors ◽  
Viral Infections ◽  
Critical Role ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Structural Proteins ◽  
Viral Protease ◽  
Virus Particles ◽  
Viral Proteases ◽  
Viral Polyprotein

SUMMARY Currently, there are a number of approved antiviral agents for use in the treatment of viral infections. However, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach. Accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. Molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses by effecting the cleavage of high-molecular-weight viral polyprotein precursors to yield functional products or by catalyzing the processing of the structural proteins necessary for assembly and morphogenesis of virus particles. This review summarizes some of the important general features of virus-encoded proteases and highlights new advances and/or specific challenges that are associated with the research and development of viral protease inhibitors. Specifically, the viral proteases encoded by the herpesvirus, retrovirus, hepatitis C virus, and human rhinovirus families are discussed.

Study of NSCLC cell migration promoted by NSCLC-Derived Extracellular Vesicle using atomic force microscopy

2021 ◽  
Author(s):  
Shuwei Wang ◽  
Jiajia Wang ◽  
Tuoyu Ju ◽  
Kaige Qu ◽  
Fan Yang ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Cell Migration ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Extracellular Vesicle ◽  
Cancer Microenvironment ◽  
Biological Processes ◽  
Force Microscopy ◽  
Atomic Force ◽  
Cellular Components

Extracellular Vesicles (EVs) secreted by cancer cells have a key role in the cancer microenvironment and progression. Previous studies have mainly focused on molecular functions, cellular components and biological processes...

scholarly journals PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jingliang Zhang ◽  
Chenyu Zhang ◽  
Xiaoling Chen ◽  
Bingwei Wang ◽  
Weining Ma ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neuronal Excitability ◽  
Granule Cells ◽  
Critical Role ◽  
Intrinsic Excitability ◽  
Seizure Susceptibility ◽  
Seizure Onset ◽  
Potential Therapeutic Target ◽  
Seizure Model

AbstractTemporal lobe epilepsy (TLE) is one of the most common and intractable neurological disorders in adults. Dysfunctional PKA signaling is causally linked to the TLE. However, the mechanism underlying PKA involves in epileptogenesis is still poorly understood. In the present study, we found the autophosphorylation level at serine 114 site (serine 112 site in mice) of PKA-RIIβ subunit was robustly decreased in the epileptic foci obtained from both surgical specimens of TLE patients and seizure model mice. The p-RIIβ level was negatively correlated with the activities of PKA. Notably, by using a P-site mutant that cannot be autophosphorylated and thus results in the released catalytic subunit to exert persistent phosphorylation, an increase in PKA activities through transduction with AAV-RIIβ-S112A in hippocampal DG granule cells decreased mIPSC frequency but not mEPSC, enhanced neuronal intrinsic excitability and seizure susceptibility. In contrast, a reduction of PKA activities by RIIβ knockout led to an increased mIPSC frequency, a reduction in neuronal excitability, and mice less prone to experimental seizure onset. Collectively, our data demonstrated that the autophosphorylation of RIIβ subunit plays a critical role in controlling neuronal and network excitabilities by regulating the activities of PKA, providing a potential therapeutic target for TLE.

scholarly journals Comprehensive analysis of lncRNA and mRNA based on expression microarray profiling reveals different characteristics of osteoarthritis between Tibetan and Han patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Junming Luo ◽  
Xiaoqin Luo ◽  
Zhili Duan ◽  
Wenbin Bai ◽  
Xiaoming Che ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathways ◽  
Critical Role ◽  
Joint Disease ◽  
Biological Processes ◽  
Expression Microarray ◽  
Chinese Han ◽  
Microarray Profiling ◽  
Trans Regulation ◽  
Mrna Expression Profiling

Abstract Background Osteoarthritis (OA) is thought to be the most prevalent chronic joint disease, especially in Tibet of China. Here, we aimed to explore the integrative lncRNA and mRNA landscape between the OA patients of Tibet and Han. Methods The lncRNA and mRNA expression microarray profiling was performed by SurePrint G3 Human Gene Expression 8x60K v2 Microarray in articular cartilage samples from OA patients of Han nationality and Tibetans, followed by GO, KEGG, and trans-regulation and cis-regulation analysis of lncRNA and mRNA. Results We found a total of 117 lncRNAs and 297 mRNAs differently expressed in the cartilage tissues of Tibetans (n = 5) comparing with those of Chinese Han (n = 3), in which 49 lncRNAs and 158 mRNAs were upregulated, and 68 lncRNAs and 139 mRNAs were downregulated. GO and KEGG analysis showed that several unreported biological processes and signaling pathways were particularly identified. LncRNA-mRNA co-expression analysis revealed a remarkable lncRNA-mRNA relationship, in which OTOA may play a critical role in the different mechanisms of the OA progression between Tibetans and Chinese Han. Conclusion This study identified different lncRNA/mRNA expression profiling between OA patients of Tibetans and Han, which were involved in many characteristic biological processes and signaling pathways.

scholarly journals Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 791
Author(s):  
Qi Liu ◽  
Bayonle Aminu ◽  
Olivia Roscow ◽  
Wei Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Therapeutic Agents ◽  
Biological Processes ◽  
Post Translational Modification ◽  
E3 Ligases ◽  
Tumor Microenvironments ◽  
Cellular Immune ◽  
Ubiquitin Conjugating Enzymes ◽  
Cellular Components

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.

scholarly journals The Yin and Yang of tumour-derived extracellular vesicles in tumour immunity

2020 ◽  
Author(s):  
Takayoshi Yamauchi ◽  
Toshiro Moroishi
Keyword(s):  
Extracellular Vesicles ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Host Immunity ◽  
Biological Processes ◽  
Small Particles ◽  
Tumour Immunity ◽  
Heterogeneous Nature ◽  
Yin And Yang ◽  
Cellular Components

Abstract Extracellular vesicles (EVs) are small particles that are naturally released from various types of cells. EVs contain a wide variety of cellular components, such as proteins, nucleic acids, lipids and metabolites, which facilitate intercellular communication in diverse biological processes. In the tumour microenvironment, EVs have been shown to play important roles in tumour progression, including immune system–tumour interactions. Although previous studies have convincingly demonstrated the immunosuppressive functions of tumour-derived EVs, some studies have suggested that tumour-derived EVs can also stimulate host immunity, especially in therapeutic conditions. Recent studies have revealed the heterogeneous nature of EVs with different structural and biological characteristics that may account for the divergent functions of EVs in tumour immunity. In this review article, we provide a brief summary of our current understanding of tumour-derived EVs in immune activation and inhibition. We also highlight the emerging utility of EVs in the diagnosis and treatment of cancers and discuss the potential clinical applications of tumour-derived EVs.

Abstract TP406: Ipsilesional Myelination is Impaired in Children With Perinatal Arterial Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Sabrina Yu ◽  
Helen Carlson ◽  
Adam Kirton
Keyword(s):  
Brain Injury ◽  
Neurological Disorders ◽  
Repeated Measures ◽  
Population Based ◽  
T Test ◽  
Biological Processes ◽  
Typically Developing ◽  
Inclusion Criteria ◽  
Perinatal Brain Injury ◽  
Perinatal Stroke

Introduction: Stroke is a leading cause of perinatal brain injury and cerebral palsy. Current therapeutic efforts focus on optimizing developmental curves but the biological processes dictating these outcomes are poorly understood. Alterations in myelination are recognized as a major determinant of outcome in preterm brain injury but are unexplored in perinatal stroke (PS). Hypothesis: Ipsilesional delays in myelination occur in children with PS and are associated with poor developmental outcome. Methods: Participants were identified through the Alberta Perinatal Stroke Project, a population-based research cohort. Inclusion criteria were: 1) MRI-confirmed, unilateral arterial PS, 2) T1-weighted MRI >6mo, 3) absence of other neurological disorders, 4) neurological outcome (Pediatric Stroke Outcome Measure, PSOM), and 5) motor assessments (Assisting Hand Assessment, AHA; Melbourne Assessment). FreeSurfer software measured hemispheric asymmetry in myelination intensity. A second method using ImageJ validated the detection of myelination asymmetry. Overall PSOM scores were classified as poor (>1) or not. Repeated measures ANOVA compared perilesional, ipsilesional remote, and contralesional homologous regions. Myelination ratios for stroke cases were compared to typically developing controls (t-test), PSOM scores (t-test), and motor assessments (Pearson’s correlation). Results: Nineteen arterial stroke cases (mean age: 13.73±4.0yo) and 27 controls (mean age: 12.52±3.7yo) were studied. Stroke cases showed a greater degree of asymmetry with lower myelination in the lesioned hemisphere, compared to controls (p<0.001). Myelination in perilesional regions was decreased compared to ipsilesional remote (p<0.001) and contralesional homologous areas (p<0.001). Ipsilesional remote regions were decreased compared to homologous regions on the contralesional hemisphere (p=0.009). Contralesional myelination was also less than controls (p<0.001). Myelination ratios were not associated with PSOM, AHA, or Melbourne scores (p=0.144, 0.218, 0.366 respectively). Conclusion: Myelination of uninjured brain in the lesioned hemisphere is altered in children with PS. Further study is required to determine clinical significance.

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