In this review we examine the functionally diverse ATPase associated with various cellular activities (AAA-ATPase), valosin-containing protein (VCP/p97), its molecular functions, the mutational landscape of VCP and the phenotypic manifestation of VCP disease. VCP is crucial to a multitude of cellular functions including protein quality control, endoplasmic reticulum-associated degradation (ERAD), autophagy, mitophagy, lysophagy, stress granule formation and clearance, DNA replication and mitosis, DNA damage response including nucleotide excision repair, ATM- and ATR-mediated damage response, homologous repair and non-homologous end joining. VCP variants cause multisystem proteinopathy, and pathology can arise in several tissue types such as skeletal muscle, bone, brain, motor neurons, sensory neurons and possibly cardiac muscle, with the disease course being challenging to predict.

Alzheimer\'s disease (AD) is the most common form of dementia. The physiopathology of AD is well described by the presence of two neuropathological features: amyloid plaques and tau neurofibrillary tangles. In the last decade, neuroinflammation and cellular stress have gained importance as key factors in the development and pathology of AD. Chronic cellular stress occurs in degenerating neurons. Stress Granules (SGs) are nonmembranous organelles formed as a response to stress, with a protective role; however, SGs have been noted to turn into pathological and neurotoxic features when stress is chronic, and they are related to an increased tau aggregation. On the other hand, correct lipid metabolism is essential to good function of the brain; apolipoproteins are highly associated with risk of AD, and impaired cholesterol efflux and lipid transport are associated with an increased risk of AD. In this review, we provide an insight into the relationship between cellular stress, SGs, protein aggregation, and lipid metabolism in AD.

BACKGROUND: Stress granules (SGs) are the dense granules formed in the cytoplasm of eukaryotic cells in response to stress stimuli, such as endoplasmic reticulum stress, heat shock, hypoxia, and arsenate exposure. Although SGs have been attracting a lot of research attention, there is still a lack of systematic analysis of SGs in the literature.
METHODS: By analyzing the literature published in the Web of Science database using the R software, we extracted all the information related to SGs from the literature and cited references. The following information was included: publications per year, overall citations, top 10 countries, top 10 authors, co-author collaborations, top 10 institutions, critical areas, and top 10 cited research articles.
RESULTS: A total of 4052 articles related to SGs were selected and screened. These documents have been cited a total of 110,553 times, with an H-index of 126 and an average of 27.28 citations per article. The authors of the literature included in this study were from 89 different countries/regions. The United States and China had the highest number of publications and ranking institutions.
CONCLUSIONS: This article presents essential insights on the characteristics and influence of SGs, demonstrating their indispensable role in immune regulation and other fields.

Ras-GTPase-activating protein binding protein 1 (G3BP1) is a multifunctional binding protein involved in a variety of biological functions, including cell proliferation, metastasis, apoptosis, differentiation and RNA metabolism. It has been revealed that G3BP1, as an antiviral factor, can interact with viral proteins and regulate the assembly of stress granules (SGs), which can inhibit viral replication. Furthermore, several viruses have the ability to hijack G3BP1 as a cofactor, recruiting translation initiation factors to promote viral proliferation. However, many functions of G3BP1 are associated with other diseases. In various cancers, G3BP1 is a cancer-promoting factor, which can promote the proliferation, invasion and metastasis of cancer cells. Moreover, compared with normal tissues, G3BP1 expression is higher in tumor tissues, indicating that it can be used as an indicator for cancer diagnosis. In this review, the structure of G3BP1 and the regulation of G3BP1 in multiple dimensions are described. In addition, the effects and potential mechanisms of G3BP1 on various carcinomas, viral infections, nervous system diseases and cardiovascular diseases are elucidated, which may provide a direction for clinical applications of G3BP1 in the future.

Under unfavorable environmental conditions, eukaryotic cells may form stress granules (SGs) in the cytosol to protect against injury and promote cell survival. The initiation, mRNA and protein composition, distribution and degradation of SGs are subject to multiple intracellular post‑translational modifications and signaling pathways to cope with stress damage. Despite accumulated comprehensive knowledge of their composition and dynamics, the function of SGs remains poorly understood. When the stress persists, aberrant and/or persistent intracellular SGs and aggregation of SGs‑related proteins may lead to various diseases. In the present article, the research progress regarding the generation, modification and function of SGs was reviewed. The regulatory effects and influencing factors of SGs in the development of tumors, cardiovascular diseases, viral infections and neurodegenerative diseases were also summarized, which may provide novel insight for preventing and treating SG‑related diseases.

The assembly of stress granules (SGs) is a well-known cellular strategy for reducing stress-related damage and promoting cell survival. SGs have become important players in human health, in addition to their fundamental role in the stress response. The critical role of SGs in cancer cells in formation, progression, and metastasis makes sense. Recent researchers have found that several SG components play a role in tumorigenesis and cancer metastasis via tumor-associated signaling pathways and other mechanisms. Gene-ontology analysis revealed the role of these protein components in the structure of SGs. Involvement in the translation process, regulation of mRNA stability, and action in both the cytoplasm and nucleus are among the main features of SG proteins. The present scoping review aimed to consider all studies on the effect of SGs on cancer formation, proliferation, and metastasis and performed based on a six-stage methodology structure and the PRISMA guideline. A systematic search of seven databases for qualified articles was conducted before July 2021. Publications were screened, and quantitative and qualitative analysis was performed on the extracted data. Go analysis was performed on seventy-one SGs protein components. Remarkably G3BP1, TIA1, TIAR, and YB1 have the largest share among the proteins considered in the studies. Altogether, this scoping review tries to demonstrate and provide a comprehensive summary of the role of SGs in the formation, progression, and metastasis of cancer by reviewing all studies.

Cytoplasmic ribonucleoproteins called stress granules (SGs) are considered as one of the main cellular solutions against stress. Their temporary presence ends with stress relief. Any factor such as chronic stress or mutations in the structure of the components of SGs that lead to their permanent presence can affect their interactions with pathological aggregations and increase the degenerative effects. SGs involved in RNA mechanisms are important factors in the pathophysiology of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and Alzheimer\'s diseases (AD). Although many studies have been performed in the field of SGs and neurodegenerative disorders, so far, no systematic studies have been executed in this field. The purpose of this study is to provide a comprehensive perspective of all studies about the role of SGs in the pathogenesis of neurodegenerative disorders with a focus on the protein ingredients of these granules. This scoping review is based on a six-stage methodology structure and the PRISMA guideline. A systematic search of seven databases for qualified articles was conducted until December 2020. Publications were screened independently by two reviewers and quantitative and qualitative analysis was performed on the extracted data. Bioinformatics analysis was used to plot the network and predict interprotein interactions. In addition, GO analysis was performed. A total of 48 articles were identified that comply the inclusion criteria. Most studies on neurodegenerative diseases have been conducted on ALS, AD, and FTD using human post mortem tissues. Human derived cell line studies have been used only in ALS. A total 29 genes of protein components of SGs have been studied, the most important of which are TDP-43, TIA-1, PABP-1. Bioinformatics studies have predicted 15 proteins to interact with the protein components of SGs, which may be the constituents of SGs. Understanding the interactions between SGs and pathological aggregations in neurodegenerative diseases can provide new targets for treatment of these disorders.

Ras-GTPase-activating protein (SH3 domain)-binding proteins (G3BPs, also known as Rasputin) are a family of RNA binding proteins that regulate gene expression in response to environmental stresses by controlling mRNA stability and translation. G3BPs appear to facilitate this activity through their role in stress granules for which they are considered a core component, however, it should be noted that not all stress granules contain G3BPs and this appears to be contextual depending on the environmental stress and the cell type. Although the role of G3BPs in stress granules appears to be one of its major roles, data also strongly suggests that they interact with mRNAs outside of stress granules to regulate gene expression. G3BPs have been implicated in several diseases including cancer progression, invasion, and metastasis as well as virus survival. There is now a body of evidence that suggests targeting of G3BPs could be explored as a form of cancer therapeutic. This review discusses the important discoveries and advancements made in the field of G3BPs biology over the last two decades including their roles in RNA stability, translational control of cellular transcripts, stress granule formation, cancer progression and its interactions with viruses during infection. An emerging theme for G3BPs is their ability to regulate gene expression in response to environmental stimuli, disease progression and virus infection making it an intriguing target for disease therapies.

Over the last few years, many reports have defined several types of RNA cell granules composed of proteins and messenger RNA (mRNA) that regulate gene expression on a post-transcriptional level. Processing bodies (P-bodies) and stress granules (SGs) are among the best-known RNA granules, only detectable when they accumulate into very dynamic cytosolic foci. Recently, a tight association has been found between positive-stranded RNA viruses, including hepatitis C virus (HCV), and these granules. The present article offers a comprehensive review on the complex and paradoxical relationship between HCV, P-bodies and SGs from a translational perspective. Despite the fact that components of P-bodies and SGs have assiduously controlled mRNA expression, either by sequestration or degradation, for thousands of years, HCV has learned how to dangerously exploit certain of them for its own benefit in an endless biological war. Thus, HCV has gained the ability to hack ancient host machineries inherited from prokaryotic times. While P-bodies and SGs are crucial to the HCV cycle, in the interferon-free era we still lack detailed knowledge of the mechanisms involved, processes that may underlie the long-term complications of HCV infection.