OTULIN Interactome Reveals Immune Response and Autophagy Associated with Tauopathy in a Mouse Model DOI Creative Commons
Ling Li, Mingqi Li, Yuyang Zhou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Abstract Tauopathies are neurodegenerative diseases that pathologically characterized by accumulation of misfolded microtubule-associated protein tau aggregates in the brain. Deubiquitination, particularly OTULIN, a unique deubiquitinase targeting methionine-1 (M1) linkages from linear ubiquitin chain assembly complex (LUBAC)), is reportedly associated with neurotoxic proteins several diseases, likely including tauopathies. To investigate potential roles OTULIN tauopathies, we analyzed interactome hippocampal tissues PS19 transgenic (Tg) mice and their non-transgenic (nTg) littermate controls using affinity purification-mass spectrometry (AP-MS). We identified 705 800 enriched Tg nTg samples, respectively, false discovery rate (FDR) <1%. Of these, 189 205 were classified as probable interactors groups, based on Significance Analysis INTeractome (SAINT) score ≥0.80 FDR ≤ 5%. A total 84 group, while 100 controls. Functional enrichment analyses revealed OTULIN-interacting group pathways related to spliceosome, complement coagulation cascades, ribosome, whereas those immune response autophagy. These findings suggest may play critical role pathogenesis tauopathy this mouse model. Highlights analyzed. ribosome. implicated ATP2A2 an specifically enhanced mice.

Language: Английский

The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation DOI Creative Commons
Mohammad Sobhan Karvandi, Farzam Sheikhzadeh Hesari, Amir Reza Aref

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Language: Английский

Citations

46
Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis in the Pathology of Alzheimer’s Disease DOI
Bidemi Emmanuel Ekundayo, Tajudeen Olabisi Obafemi, Olusola Bolaji Adewale

et al.

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(2), P. 457 - 477

Published: March 12, 2024

Language: Английский

Citations

32
The neuropathobiology of multiple sclerosis DOI
Marcel S. Woo, Jan Broder Engler, Manuel A. Friese

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(7), P. 493 - 513

Published: May 24, 2024

Language: Английский

Citations

29
Redox changes and cellular senescence in Alzheimer's disease DOI Creative Commons

Nicole Yu,

Mazhar Pasha, John Jia En Chua

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103048 - 103048

Published: Jan. 17, 2024

The redox process and cellular senescence are involved in a range of essential physiological functions. However, they also implicated pathological processes underlying age-related neurodegenerative disorders, including Alzheimer's disease (AD). Elevated levels reactive oxygen species (ROS) generated as result abnormal accumulation beta-amyloid peptide (Aβ), tau protein, heme dyshomeostasis is further aggravated by mitochondria dysfunction endoplasmic reticulum (ER) stress. Excessive ROS damages vital components such proteins, DNA lipids. Such damage eventually leads to impaired neuronal function cell death. Heightened oxidative stress can induce via activation the senescence-associated secretory phenotype exacerbate inflammation tissue dysfunction. In this review, we focus on how changes system contribute AD affected perturbations metabolism mitochondrial function. While potential therapeutic strategies targeting have received some attention, more research necessary bring them into clinical application.

Language: Английский

Citations

26
Artemisinin Alleviates Astrocyte Overactivation and Neuroinflammation by Modulating the IRE1/NF-κB Signaling Pathway in In Vitro and In Vivo Alzheimer's Disease Models DOI
Lei Chen, Xia Zhao, Rui Sheng

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 229, P. 96 - 110

Published: Jan. 16, 2025

Language: Английский

Citations

2
The endoplasmic reticulum stress and unfolded protein response in Alzheimer’s disease: A calcium dyshomeostasis perspective DOI Creative Commons
Dmitry Lim, Laura Tapella, Giulia Dematteis

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101914 - 101914

Published: March 21, 2023

Protein misfolding is prominent in early cellular pathology of Alzheimer's disease (AD), implicating pathophysiological significance endoplasmic reticulum stress/unfolded protein response (ER stress/UPR) and highlighting it as a target for drug development. Experimental data from animal AD models observations on human specimens are, however, inconsistent. ER stress associated UPR are readily observed vitro some model animals. In the brain, components markers well transducers at Braak stages III-VI with severe neuropathology neuronal death. The picture, further complicated by brain region- cell type-specificity AD-related pathology. Terms 'disturbed' or 'non-canonical' stress/UPR were used to describe discrepancies between experimental classic cascade. Here we discuss possible 'disturbing' 'interfering' factors which may modify pathogenesis. We focus dysregulation Ca2+ homeostasis, store-operated entry, interaction mitochondria. suggest that detailed study CNS type-specific alterations homeostasis deepen our understanding dysproteostasis.

Language: Английский

Citations

38
Interlink between the gut microbiota and inflammation in the context of oxidative stress in Alzheimer’s disease progression DOI Creative Commons
Tushar Kanti Das, Bhanu Priya Ganesh

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: May 1, 2023

The microbiota-gut-brain axis is an important pathway of communication and may dynamically contribute to Alzheimer's disease (AD) pathogenesis. Pathological commensal gut microbiota alterations, termed as dysbiosis, can influence intestinal permeability break the blood-brain barrier which trigger AD pathogenesis via redox signaling, neuronal, immune, metabolic pathways. Dysbiosis increases oxidative stress. Oxidants affect innate immune system through recognizing microbial-derived pathogens by Toll-like receptors initiating inflammatory process. Most microbiome research work highlights relationship between AD, but contributory connection precise bacteria brain dysfunction in pathology cannot be fully demonstrated. Here, we summarize current information fundamental connections stress, inflammation, dysbiosis AD. This review emphasizes on involvement regulation responses including central peripheral cross-talk. It provides insights for novel preventative therapeutic approaches

Language: Английский

Citations

36
Endoplasmic reticulum stress in Alzheimer's disease: Molecular mechanisms and therapeutic prospects DOI

Pushank Nagar,

Prajjwal Sharma,

Rishika Dhapola

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 330, P. 121983 - 121983

Published: July 29, 2023

Language: Английский

Citations

32
Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity DOI Creative Commons
Nicola Marrano, Giuseppina Biondi, Anna Borrelli

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(1), P. 183 - 183

Published: Jan. 16, 2023

Type 2 diabetes (T2D) and Alzheimer’s diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates AD is a significant comorbidity of T2D, there ~1.4–2-fold increase risk developing among T2D patients, involvement possible common triggers pathogenesis these two remains largely unknown. Of note, recent mechanistic insights suggest lipotoxicity could missing ring pathogenetic mechanisms linking to AD. Indeed, obesity, which represents main cause lipotoxicity, has been recognized as factor for both pathological conditions. Lipotoxicity can lead inflammation, insulin resistance, oxidative stress, ceramide amyloid accumulation, endoplasmic reticulum ferroptosis, autophagy, are shared biological events In current review, we try provide critical comprehensive view molecular pathways activated by AD, attempting summarize how drive future research open way new therapeutic perspectives.

Language: Английский

Citations

25
Gene networks and systems biology in Alzheimer's disease: Insights from multi‐omics approaches DOI Creative Commons
Negin Rahimzadeh, Shushrruth Sai Srinivasan, Jing Zhang

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(5), P. 3587 - 3605

Published: March 27, 2024

Despite numerous studies in the field of dementia and Alzheimer's disease (AD), a comprehensive understanding this devastating remains elusive. Bulk transcriptomics have provided insights into underlying genetic factors at high level. Subsequent technological advancements focused on single-cell omics, encompassing techniques such as RNA sequencing epigenomics, enabling capture transcripts chromatin states single cell or nucleus resolution. Furthermore, emergence spatial omics has allowed study gene responses vicinity amyloid beta plaques across various brain regions. With vast amount data generated, utilizing regulatory networks to comprehensively become essential. This review delves some employed AD, explores discoveries made using these techniques, provides future field.

Language: Английский

Citations

9