Stress Granules and Neurodegenerative Disorders: A Scoping Review

Abstract

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.

mTORC1 Crosstalk With Stress Granules in Aging and Age-Related Diseases

“…Neurodegeneration and cancer are age-related diseases associated with senescence ( Baker and Petersen, 2018 ; Sikora et al, 2021 ). Both aberrant mTORC1 activity ( Chrienova et al, 2021 ; Querfurth and Lee, 2021 ) and chronic SG formation ( Wolozin and Ivanov, 2019 ; Asadi et al, 2021 ) link with neurodegenerative diseases including ALS (amyotrophic lateral sclerosis), FTD (frontotemporal dementia), AD (Alzheimer’s disease) or PD (Parkinson’s disease). However, their crosstalk in neurodegenerative diseases is largely unknown.…”

Analysis of ROQUIN, Tristetraprolin (TTP), and BDNF/miR-16/TTP regulatory axis in late onset Alzheimer’s disease

“…MSUT2, also known as the mammalian suppressor of tau pathology-2, binds to the polyadenosine tail (poly[A]-tail) of mRNAs through the zinc-finger domain CCCH-type at its C-terminal, leading to the formation of pathological tau protein ( Baker et al, 2020 ). Tau proteins are a collection of six protein isoforms generated by alternative splicing of the microtubule-associated protein tau (MAPT) gene, and their major role is to preserve the integrity of microtubules in axons owing to their high expression in CNS neurons ( Asadi et al, 2021 ). In addition, loss of MSUT2 function can reduce tau protein formation and prevent neuronal death, but the molecular mechanism is still unclear, and the only conjecture that can be made is the shared function of MSUT2 and PABPN1 ( Baker et al, 2020 ).…”

Tau mRNA Metabolism in Neurodegenerative Diseases: A Tangle Journey

“…Additionally, SGs are known to be constituted by mRNAs, RNA binding proteins, the small 40S ribosome subunit and translation factors [ 170 , 171 , 172 ]. Moreover, SGs can regulate mRNA metabolism and protein translation [ 173 ]. Concerning tauopathies, TIA1 reduction was able to prolong the lifetimes and increased neuronal survival in transgenic P301S tau mice [ 162 ].…”