Zinc Finger Proteins in Neuro-Related Diseases Progression

Bu, Siyuan; Lv, Yihan; Liu, Yusheng; Qiao, Sen; Wang, Hongmei

doi:10.3389/fnins.2021.760567

Cited by 59 publications

(50 citation statements)

References 148 publications

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“…The main function of ZFs in the brain is to promote the development of different parts of the brain and the differentiation of neural stem cells. Many studies have shown that ZFPs are closely related to the pathogenesis of nervous system diseases [ 170 ]. Researchers found that many ZFP DNA-binding domains downregulated the transcriptional activity of nr2f through missense mutations, to regulate cognitive impairment and optic nerve atrophy [ 171 ].…”

Section: Zfp and The Cellular Pathwaysmentioning

confidence: 99%

Zinc in Cognitive Impairment and Aging

et al. 2022

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Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes in normal mammalian brain development, especially in the development of the central nervous system. Zinc deficiency can lead to neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular diseases, and other pathological conditions, which can cause cognitive impairment and premature aging. This study aimed to review the important effects of zinc and zinc-associated proteins in cognitive impairment and aging, to reveal its molecular mechanism, and to highlight potential interventions for zinc-associated aging and cognitive impairments.

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Section: Zfp and The Cellular Pathwaysmentioning

confidence: 99%

Zinc in Cognitive Impairment and Aging

et al. 2022

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“…On the other hand, TTP has an increased expression in TC samples compared to healthy controls. So far, studies on other types of zinc-finger family proteins (C2H2 type, MYM type, ZC3H14 type, and Matrin type) have been performed in AD (reviewed in Bu et al, 2021 ). Meanwhile, MSUT2 (ZC3H14), belonging to the CCCH family, ultimately affects the accumulation of tau proteins to affect NFTs ( Baker et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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

Asadi

Talebi

Gharesouran

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a heterogeneous degenerative disorder of the brain that is on the rise worldwide. One of the critical processes that might be disturbed in AD is gene expression regulation. Tristetraprolin (TTP) and RC3H1 gene (ROQUIN) are two RNA-binding proteins (RBPs) that target AU-rich elements (AREs) and constitutive decay elements (CDEs), respectively. TTP and ROQUIN, members of the CCCH zinc-finger protein family, have been demonstrated to fine-tune numerous inflammatory factors. In addition, miR-16 has distinct characteristics and may influence the target mRNA through the ARE site. Interestingly, BDNF mRNA has ARE sites in the 3’ untranslated region (UTR) and can be targeted by regulatory factors, such as TTP and miR-16 on MRE sequences, forming BDNF/miR-16/TTP regulatory axis. A number of two microarray datasets were downloaded, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD and corresponding controls. R software was used to identify BDNF, TTP, ROQUIN, and miR-16 expression levels in temporal cortex (TC) tissue datasets. Q-PCR was also used to evaluate the expression of these regulatory factors and the expression of BDNF in the blood of 50 patients with AD and 50 controls. Bioinformatic evaluation showed that TTP and miR-16 overexpression might act as post-transcriptional regulatory factors to control BDNF expression in AD in TC samples. Instead, this expression pattern was not found in peripheral blood samples from patients with AD compared to normal controls. ROQUIN expression was increased in the peripheral blood of patients with AD. Hsa-miR-16-5p levels did not show significant differences in peripheral blood samples. Finally, it was shown that TTP and BDNF, based on evaluating the receiver operating characteristic (ROC), effectively identify patients with AD from healthy controls. This study could provide a new perspective on the molecular regulatory processes associated with AD pathogenic mechanisms linked to the BDNF growth factor, although further research is needed on the possible roles of these factors in AD.

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“…The zinc-finger units regulate gene expression at the transcriptional and translational levels and are highly expressed in the brain (48). It has already been demonstrated that zinc-finger genes are associated with pathological changes in AD and regulate the expression of AD-related genes that are upstream in the production of hyperphosphorylated tau (49). This could explain the positive association when integrating [ 18 F]FDG-PET and zinc-finger-related regulatory units enriched with DEGs.…”

Section: Discussionmentioning

confidence: 99%

Serine/threonine kinase activity associates with brain glucose metabolism changes in Alzheimer’s Disease

Povala

Bastiani

Bellaver

et al. 2022

Preprint

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Positron emission tomography (PET) imaging has greatly improved the diagnosis and monitoring of Alzheimer's disease (AD). The recently developed neuroinformatic field is expanding analytical and computational strategies to study multimodal neuroscience data. One approach is integrating PET imaging and omics to provide new insights into AD pathophysiology. Hippocampal and blood transcriptomic data of cognitively unimpaired (CU) and cognitively impaired (CI) individuals were obtained from Gene Expression Omnibus (GEO) databases and the Alzheimer's Disease Neuroimaging Initiative (ADNI). We used the differentially expressed genes (DEGs) from these datasets to implement a modular dimension reduction approach based on Gene Ontology (GO) and reverse engineering of transcriptional networks centered on transcription factors (TF). GO clusters and regulatory units of TF were selected to undergo integration with [18F]Fluorodeoxyglucose ([18F]FDG)-PET images using voxel-wise linear regression models adjusted for age, gender, years of education, and APOEϵ4 status. The GO semantic similarity resulted in 16 GO clusters enriched with overlapping DEGs in blood and the brain. Voxel-wise analysis revealed a strong association between the cluster related to the regulation of protein serine/threonine kinase activity and the [18F]FDG-PET signal in the brain. The master regulator analysis showed 61 regulatory units of TF significantly enriched with DEGs. The voxel-wise analysis of these regulons showed that zinc-finger-related regulatory units had the closest association with brain glucose metabolism. We identified multiple biological processes and regulatory units of TF associated with [18F]FDG-PET metabolism in the brain of individuals across the aging and AD clinical spectrum. Furthermore, the prominent enrichment of protein serine/threonine kinase activity-related GO cluster and the zinc-finger-related regulatory units highlight the potential gene signatures associated with changes in glucose metabolism due to AD pathology.

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Zinc Finger Proteins in Neuro-Related Diseases Progression

Cited by 59 publications

References 148 publications

Zinc in Cognitive Impairment and Aging

Zinc in Cognitive Impairment and Aging

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

Serine/threonine kinase activity associates with brain glucose metabolism changes in Alzheimer’s Disease

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