Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells

Volume 2 (2018)

Cover: This month in Cell Stress: Kinase signaling in the innate immune system. Fluorescence microscopic depiction of immune cell responses within the CNS upon chronic pain. Images by Centre for Nanoscale BioPhotonics (CNBP) licensed under the CC BY 2.0 license. Image modified by Cell Stress. The cover is published under the CC BY 4.0 license.

Salmonella Typhimurium infection: Type I Interferons integrate cellular networks to disintegrate macrophages

Nirmal Robinson^1,2

Salmonella enterica serovar Typhimurium (S. Typhimurium) are facultative intracellular bacteria that effectively evade innate immune defense mechanisms using a plethora of pathogenic principles encoded in their pathogenicity islands namely Salmonella

Centriolar satellites prevent uncontrolled degradation of centrosome proteins: a speculative review

Nicolas Lecland¹ and Andreas Merdes¹

INTRODUCTION Centrosomes are cytoplasmic structures that serve as primary microtubule organizing centers in a large variety of animal cells. They consist of a pair of cylindrically shaped centrioles, surrounded by

miR34a: a master regulator in the pathogenesis of bronchopulmonary dysplasia

Pragnya Das¹, Mansoor Ali Syed^1,2, Dilip Shah¹, Vineet Bhandari^1,3,*

BPD has been getting more attention as neonatologists from across the world are getting better in saving the lives of premature neonates. This has mobilized intense research to fill the

Novel role of the SIRT4-OPA1 axis in mitochondrial quality control

Alexander Lang¹ and Roland P. Piekorz¹

Aging is defined by various molecular and cellular hallmarks, among them stem cell exhaustion, genomic instability, altered proteostasis, cellular senescence, and mitochondrial dysfunction [cite]10.1016/j.cell.2013.05.039[/cite]. Mitochondrial defects are considered major drivers

MST kinases in innate immune signaling

Zhubing Shi¹ and Zhaocai Zhou^1,2

The mammalian STE20-like (MST) protein kinases are composed of MST1, MST2, MST3, MST4 and YSK1. They play crucial roles in cell growth, migration, polarity and apoptosis. Dysfunction of these kinases often leads to diseases. MST kinases are extensively involved in development and function of immune system. Here, we review recent progresses on the regulatory function of MST kinases in innate immune signaling.

Therapeutic potential of HDAC6 in amyotrophic lateral sclerosis

Wenting Guo^1,2 and Ludo Van Den Bosch^1,2

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective death of motor neurons in the motor cortex, brainstem and spinal cord. This leads to progressive muscle weakness,

Targeting Nfix to fix muscular dystrophies

Giuliana Rossi¹, Valentina Taglietti² and Graziella Messina²

A shared knowledge in the field is that to be really successful, any therapeutic strategy has to rely on good muscle quality. In fact, there is no available approach able

p53 and energy balance: meeting hypothalamic AgRP neurons

Omar Al-Massadi^1,2,#, Mar Quiñones^1,2,#, Ruben Nogueiras^1,2

Cancer cells undergo profound metabolic changes to cope with the high energy demand for cell growth and division. Given the importance of this metabolic reprogramming in tumor development, it seems

Attenuating MKRN1 E3 ligase-mediated AMPKα suppression increases tolerance against metabolic stresses in mice

Hyunji Han¹, Sehyun Chae², Daehee Hwang^2,3 and Jaewhan Song¹

The signaling pathways instigated by the activation of AMP-activated protein kinase (AMPK) play major roles in balancing the energy levels in cells as well as in the whole-body system by

p38β MAPK mediates ULK1-dependent induction of autophagy in skeletal muscle of tumor-bearing mice

Zhelong Liu^{1, 2,†}, Ka Wai Thomas Sin^1,†, Hui Ding^1,3, HoangAnh Amy Doan¹, Song Gao¹, Hongyu Miao⁴, Yahui Wei^1,#, Yiman Wang^1,#, Guohua Zhang¹, and Yi-Ping Li¹

INTRODUCTION Cancer has been increasingly recognized as a systemic disorder that stresses multiple organs independent of its location. At least 50% of cancer patients experience cachexia, a systemic wasting syndrome

Mitochondrial stress management: a dynamic journey

Miriam Valera-Alberni^1,2 and Carles Canto¹

Mitochondria undergo continuous challenges in the course of their life, from their generation to their degradation. These challenges include the management of reactive oxygen species, the proper assembly of mitochondrial respiratory complexes and the need to balance potential mutations in the mitochondrial DNA. The detection of damage and the ability to keep it under control is critical to fine-tune mitochondrial function to the organismal energy needs. In this review, we will analyze the multiple mechanisms that safeguard mitochondrial function in light of in crescendo damage. This sequence of events will include initial defense against excessive reactive oxygen species production, compensation mechanisms by the unfolded protein response (UPRmt), mitochondrial dynamics and elimination by mitophagy.

Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets

Konstantin Stoletov¹, Lian Willetts¹, Perrin H. Beatty¹ and John D. Lewis¹

INTRODUCTION Currently, many cancer patients undergo chemotherapy, which is aimed at mitigating the risk of future metastasis. These treatments, however, have numerous system-wide off-target effects that negatively impact the patients’

Therapeutic anti-tumor immunity directed against neo-epitopes by intratumor delivery of mRNA encoding MLKL

Lien Van Hoecke^1,2 and Xavier Saelens^1,2,3

We have developed a potentially generic treatment method to induce tumor antigen-specific cellular immunity based on the transient intra-tumor expression of the necroptosis-inducing factor MLKL (Figure 1). Importantly, we have

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Foie gras and liver regeneration: a fat dilemma

Maria Agnese Della Fazia¹ and Giuseppe Servillo¹

The liver has a unique ability of regenerating after injuries or partial loss of its mass. The mechanisms responsible for liver regeneration – mostly occurring when the hepatic tissue is damaged or functionally compromised by metabolic stress – have been studied in considerable detail over the last few decades, because this phenomenon has both basic-biology and clinical relevance. More specifically, recent interest has been focusing on the widespread occurrence of abnormal nutritional habits in the Western world that result in an increased prevalence of non-alcoholic fatty liver disease (NAFLD). NAFLD is closely associated with insulin resistance and dyslipidemia, and it represents a major clinical challenge. The disease may progress to steatohepatitis with persistent inflammation and progressive liver damage, both of which will compromise regeneration under conditions of partial hepatectomy in surgical oncology or in liver transplantation procedures. Here, we analyze the impact of ER stress and SIRT1 in lipid metabolism and in fatty liver pathology (...)

Amelioration of obesity-induced diabetes by a novel autophagy enhancer

Hyejin Lim¹ and Myung-Shik Lee¹

Our screening system was a convenient high throughput assay of autophagic flux rather than cumulative autophagy levels, and the index of autophagic activity was calculated as the ratio of the

Epigenetic mechanisms behind cellular sensitivity to DNA damage

Amanda K. Williamson¹, Zijing Zhu¹ and Zhi-Min Yuan¹

INTRODUCTION Epigenetics is the regulation of gene expression independent of the gene sequence itself via the interactions between DNA and proteins called histones [cite]10.4161/epi.24042[/cite]. In the nucleus, DNA is highly

Striatal dual cholinergic /GABAergic transmission in Parkinson disease: friends or foes?

Natalia Lozovaya¹, Yehezkel Ben-Ari¹ and Constance Hammond¹

Although constituting less than 1% of neuronal population of the striatum, cholinergic interneurons play a major role in the control of sensory integration in preparation for movements. These giant neurons

The NLRC4 inflammasome requires IRF8-dependent production of NAIPs

Ein Lee^1,2, Rajendra Karki¹ and Thirumala-Devi Kanneganti¹

Inflammasomes orchestrate cellular responses to pathogen- or danger-associated molecular patterns by controlling the activation of caspase-1. Inflammasome activation results in enzymatically active caspase-1, which mediates the maturation and release of

Targeting LRH-1/NR5A2 to treat type 1 diabetes mellitus

Nadia Cobo-Vuilleumier¹, Petra I. Lorenzo¹ and Benoit R. Gauthier¹

The liver receptor homolog-1 (LRH-1) is a member of the NR5A family of nuclear receptors that plays a pivotal role in early embryonic development while later on it specifies the

Nucleolar Stress: hallmarks, sensing mechanism and diseases

Kai Yang^1,2, Jie Yang¹ and Jing Yi¹

The nucleolus is a prominent subnuclear compartment, where ribosome biosynthesis takes place. Recently, the nucleolus has gained attention for its novel role in the regulation of cellular stress. Nucleolar stress is emerging as a new concept, which is characterized by diverse cellular insult-induced abnormalities in nucleolar structure and function, ultimately leading to activation of p53 or other stress signaling pathways and alterations in cell behavior. Despite a number of comprehensive reviews on this concept, straightforward and clear-cut way criteria for a nucleolar stress state, regarding the factors that elicit this state, the morphological and functional alterations as well as the rationale for p53 activation are still missing. Based on literature of the past two decades, we herein summarize the evolution of the concept and provide hallmarks of nucleolar stress. Along with updated information and thorough discussion of existing confusions in the field, we pay particular attention to the current understanding of the sensing mechanisms (...)

Calling RNF168 to action

Somaira Nowsheen¹ and Zhenkun Lou²

– [table id=103 /] – It is interesting to note that MDC1 acts as a node for the recruitment of both RNF8 and L3MBTL2 and brings these two factors into

Exosomal secretion of truncated cytosolic lysyl-tRNA synthetase induces inflammation during cell starvation

Sang Bum Kim^1,2, Seongmin Cho^{1, 2} and Sunghoon Kim^1,2

Kim et al. (2017) reveals three crucial steps of KRS secretion, including its dissociation from the MSC complex, interaction with syntenin, and secretion via the exosomal pathway (Figure 1). –

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Astrocytes, emerging stars of energy homeostasis

Simonetta Camandola¹

INTRODUCTION The brain is the organ responsible for the centralized control of the other organs’ functions and, in higher vertebrates, of reasoning. Such tasks are achieved thanks to the interconnections

Base editors: a powerful tool for generating animal models of human diseases

Zongyang Lu^1,2 and Xingxu Huang^1,3

BASE EDITORS: A NOVEL GENOME ENGINEERING TOOL Genetically engineered mouse models of human diseases have long been used in understanding the underlying mechanisms of the clinically relevant genetic disorders. In

Unweaving the role of nuclear Lamins in neural circuit integrity

Samantha L. Deal¹ and Shinya Yamamoto^1,2,3,4

Structural integrity of the nuclear membrane is essential for the homeostasis of eukaryotic cells. Critical components of this process are Lamins or type-V intermediate filament proteins that form a meshwork

Alzheimer’s disease: amyloid-based pathogenesis and potential therapies

Yixiu Zhou¹, Yuhui Sun², Quan-Hong Ma² and Yaobo Liu²

INTRODUCTION Alzheimer’s disease (AD) is one of the most prevalent forms of dementia; in 2015, for example, AD affected ~46.8 million people worldwide. It is estimated that this number will

Membrane closure in stress induced-autophagosome formation

Eiji Morita¹

Autophagy (macroautophagy) is a bulk degradation system that sequesters cytoplasmic components by generating double-layered isolation membranes and delivering these isolated contents to the lysosomes [cite]10.1146/annurev-cellbio-092910-154005[/cite]. Though this pathway was originally

Centriolar satellites prevent uncontrolled degradation of centrosome proteins: a speculative review

Nicolas Lecland¹ and Andreas Merdes¹

Novel role of the SIRT4-OPA1 axis in mitochondrial quality control

Alexander Lang¹ and Roland P. Piekorz¹