The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases

Liu, Na; Lin, Miaomiao; Wang, Yan

doi:10.1007/s12035-022-03063-3

Cited by 8 publications

(4 citation statements)

References 186 publications

(218 reference statements)

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“…According to GO analysis, BP PELI1 enrichment is depicted in the Toll signaling pathway, the regulation of the necroptotic process and protein K63-and K48-linked ubiquitination (Table S14). The important role of E3 ubiquitin ligases and deubiquitinating enzymes in the pathogenesis mechanisms of neurodegenerative diseases have been extensively analyzed, such as their association with a-synuclein in Parkinson's disease, as well as their deficiency in mitophagy and mitochondrial dynamics in relation to Parkin's response [44]. ZEB2, which encodes the Zinc Finger E-Box Binding Homeobox 2 protein, significantly enriched the regulation of transforming growth factor beta receptor signaling pathway and regulation of organelle organization (Table S15).…”

Section: Resultsmentioning

confidence: 99%

Exploring Promising Biomarkers for Alzheimer’s Disease through the Computational Analysis of Peripheral Blood Single-Cell RNA Sequencing Data

et al. 2023

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Alzheimer’s disease (AD) represents one of the most important healthcare challenges of the current century, characterized as an expanding, “silent pandemic”. Recent studies suggest that the peripheral immune system may participate in AD development; however, the molecular components of these cells in AD remain poorly understood. Although single-cell RNA sequencing (scRNA-seq) offers a sufficient exploration of various biological processes at the cellular level, the number of existing works is limited, and no comprehensive machine learning (ML) analysis has yet been conducted to identify effective biomarkers in AD. Herein, we introduced a computational workflow using both deep learning and ML processes examining scRNA-seq data obtained from the peripheral blood of both Alzheimer’s disease patients with an amyloid-positive status and healthy controls with an amyloid-negative status, totaling 36,849 cells. The output of our pipeline contained transcripts ranked by their level of significance, which could serve as reliable genetic signatures of AD pathophysiology. The comprehensive functional analysis of the most dominant genes in terms of biological relevance to AD demonstrates that the proposed methodology has great potential for discovering blood-based fingerprints of the disease. Furthermore, the present approach paves the way for the application of ML techniques to scRNA-seq data from complex disorders, providing new challenges to identify key biological processes from a molecular perspective.

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Section: Resultsmentioning

confidence: 99%

Exploring Promising Biomarkers for Alzheimer’s Disease through the Computational Analysis of Peripheral Blood Single-Cell RNA Sequencing Data

et al. 2023

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“…According to study, estrogen provides neuroprotection to cortical neurons in rats via the AKt-mediated pathway (Tecalco-Cruz et al, 2023). As per study conducted by Liu et al (2023), the overexpression of ERβ was found to offer protection in PC12 cells from apoptosis caused by Aβ. However, this activity was observed to be abolished in cells that were treated with a AKt-inhibitor (Perluigi et al, 2024).…”

Section: Overexpression Of Erβmentioning

confidence: 90%

“…This is achieved through the binding of ERβ to the Bcl-2-associated death promoter (BAD), which subsequently limits the interactions of BAD with downstream targets (Fern andez et al, 2023). The findings of these inquiries furnish substantiation for the defensive function of ERβ in ameliorating neurotoxicity instigated by Aβ (Liu et al, 2023).…”

Section: Overexpression Of Erβmentioning

confidence: 97%

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Rishabh,

Rohilla,

Bansal

et al. 2024

Eur J of Neuroscience

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In females, Alzheimer's disease (AD) incidences increases as compared to males due to estrogen deficiency after menopause. Estrogen therapy is the mainstay therapy for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. Estrogen plays a crucial role in amyloid precursor protein (APP) processing and overall neuronal health by regulating various factors such as brain‐derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain‐associated protein (Daxx) translocation, glutamatergic excitotoxicity, Voltage‐Dependent Anion Channel, Insulin‐Like Growth Factor 1 Receptor, estrogen‐metabolising enzymes and apolipoprotein E (ApoE) protein polymorphisms. All these factors impact the physiology of postmenopausal women. Estrogen replacement therapies play an important treatment strategy to prevent AD after menopause. However, use of these therapies may lead to increased risks of breast cancer, venous thromboembolism and cardiovascular disease. Various therapeutic approaches have been used to mitigate the effects of estrogen on AD. These include hormone replacement therapy, Selective Estrogen Receptor Modulators (SERMs), Estrogen Receptor Beta (ERβ)‐Selective Agonists, Transdermal Estrogen Delivery, Localised Estrogen Delivery, Combination Therapies, Estrogen Metabolism Modulation and Alternative Estrogenic Compounds like genistein from soy, a notable phytoestrogen from plant sources. However, mechanism via which these approaches modulate AD in postmenopausal women has not been explained earlier thoroughly. Present review will enlighten all the molecular mechanisms of estrogen and estrogen replacement therapies in AD. Along‐with this, the association between estrogen, estrogen‐metabolising enzymes and ApoE protein polymorphisms will also be discussed in postmenopausal AD.

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“…To avoid harmful changes, the UPS and autophagy processes facilitate the degradation of unwanted misfolded proteins that would otherwise contribute to the formation of aggregates. Consistently, impairment in the UPS is often associated with neurodegenerative disorders, such as Parkinson's disease [41,42].…”

Section: Introductionmentioning

confidence: 94%

A Survey on the Expression of the Ubiquitin Proteasome System Components HECT- and RBR-E3 Ubiquitin Ligases and E2 Ubiquitin-Conjugating and E1 Ubiquitin-Activating Enzymes during Human Brain Development

Magnati,

Alladio,

Bracco

2024

IJMS

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Human brain development involves a tightly regulated sequence of events that starts shortly after conception and continues up to adolescence. Before birth, neurogenesis occurs, implying an extensive differentiation process, sustained by changes in the gene expression profile alongside proteome remodeling, regulated by the ubiquitin proteasome system (UPS) and autophagy. The latter processes rely on the selective tagging with ubiquitin of the proteins that must be disposed of. E3 ubiquitin ligases accomplish the selective recognition of the target proteins. At the late stage of neurogenesis, the brain starts to take shape, and neurons migrate to their designated locations. After birth, neuronal myelination occurs, and, in parallel, neurons form connections among each other throughout the synaptogenesis process. Due to the malfunctioning of UPS components, aberrant brain development at the very early stages leads to neurodevelopmental disorders. Through deep data mining and analysis and by taking advantage of machine learning-based models, we mapped the transcriptomic profile of the genes encoding HECT- and ring-between-ring (RBR)-E3 ubiquitin ligases as well as E2 ubiquitin-conjugating and E1 ubiquitin-activating enzymes during human brain development, from early post-conception to adulthood. The inquiry outcomes unveiled some implications for neurodevelopment-related disorders.

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The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases

Cited by 8 publications

References 186 publications

Exploring Promising Biomarkers for Alzheimer’s Disease through the Computational Analysis of Peripheral Blood Single-Cell RNA Sequencing Data

Exploring Promising Biomarkers for Alzheimer’s Disease through the Computational Analysis of Peripheral Blood Single-Cell RNA Sequencing Data

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

A Survey on the Expression of the Ubiquitin Proteasome System Components HECT- and RBR-E3 Ubiquitin Ligases and E2 Ubiquitin-Conjugating and E1 Ubiquitin-Activating Enzymes during Human Brain Development

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