Alzheimer’s Disease: An Update and Insights Into Pathophysiology

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: March 30, 2022

Alzheimer’s disease (AD) is an irreversible brain disorder associated with slow, progressive loss of functions mostly in older people. The processes start years before the symptoms are manifested at which point most therapies may not be as effective. In hippocampus, key proteins involved JAK2/STAT3 signaling pathway, such p-JAK2-Tyr1007 and p-STAT3-Tyr705 were found to elevated various models AD. addition neurons, glial cells astrocytes also play a crucial role progression Without having significant effect on tau amyloid pathologies, pathway reactive exhibits behavioral impact experimental Cholinergic atrophy AD has been traced trophic failure NGF metabolic essential for survival maintenance basal forebrain cholinergic neurons (BFCN). AD, there alteration conversion proNGF mature (mNGF), increase degradation biologically active mNGF. Thus, application exogenous mNGF studies was shown improve recovery atrophic BFCN. Furthermore, it now coming light that FGF7/FGFR2/PI3K/Akt mediated by microRNA-107 pathogenesis. Vascular dysfunction long cognitive decline increased risk factors higher cerebral beta-amyloid (Aβ) burden, while synergistically acting Aβ induce decline. apolipoprotein E4 polymorphism just one vascular factors, but prevalent genetic factor More recently, research focus shifted toward metabolisms neurotransmitters, major minor nutrients, thus giving rise metabolomics, important “omics” tool diagnosis prognosis neurodegenerative diseases based individual’s metabolome. This review will therefore proffer better understanding novel pathways neural mechanisms elaborate potential links between recent developments “omics”-based biomarkers

Language: Английский

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MicroRNAs in Alzheimer's disease: Potential diagnostic markers and therapeutic targets

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 148, P. 112681 - 112681

Published: Feb. 14, 2022

Alzheimer's disease (AD) is the most common neurodegenerative disease, with cognitive decline as primary clinical feature. According to epidemiological statistics, 50 million people worldwide are currently affected by disease. Although new drugs such aducanumab have been approved for use in treatment of AD, none them reversed progression AD. MicroRNAs (miRNAs) small molecule RNAs that exert their biological functions regulating expression intracellular proteins, and differential abundance varieties found between central peripheral tissues AD patients healthy controls. This article will summarise changes miRNAs process, potential role diagnostic markers therapeutic targets be explored.

Language: Английский

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The role of exosomes in diagnosis, pathophysiology, and management of Alzheimer's Disease

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 754, P. 151526 - 151526

Published: Feb. 22, 2025

Language: Английский

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The role of microRNAs in neurobiology and pathophysiology of the hippocampus

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Sept. 4, 2023

MicroRNAs (miRNAs) are short non-coding and well-conserved RNAs that linked to many aspects of development disorders. control the expression genes related different biological processes play a prominent role in harmonious genes. During neural central nervous system, miRNAs regulated time space. In mature brain, dynamic continues, highlighting their functional importance neurons. The hippocampus, as one crucial brain structures, is key component major connections brain. Gene abnormalities hippocampus lead disturbance neurogenesis, maturation synaptic formation. These disturbances at root several neurological disorders behavioral deficits, including Alzheimer's disease, epilepsy schizophrenia. There strong evidence contributed neurodegenerative mechanisms through imbalanced activity ion channels, neuronal excitability, plasticity apoptosis. Some affect oxidative stress, inflammation, differentiation, migration neurogenesis hippocampus. Furthermore, signaling cascades neurodegeneration, such NF-Kβ signaling, PI3/Akt Notch pathway, closely modulated by miRNAs. observations, suggest microRNAs significant regulators complicated network gene regulation current review, we focus on miRNA progression normal We also consider how for pathophysiological pathways.

Language: Английский

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Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer’s disease

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 253, P. 155007 - 155007

Published: Dec. 4, 2023

Language: Английский

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Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 18, 2024

Abstract Alzheimer’s disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced Survival gene Elimination (DISE) a mechanism mediated short (s) RNAs acting through RNA-induced silencing complex (RISC). DISE thus form of RNA interference, in which G-rich 6mer seed sequences sRNAs (position 2-7) target hundreds C-rich matches genes essential for survival, resulting activation pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound to quantify toxicity several model systems. In mouse AD models aging brain, induced pluripotent stem cell-derived neurons from patients, cells exposed Aβ42 oligomers, show shift more toxic seeds compared controls. contrast, brains “SuperAgers”, humans over age 80 who have superior memory performance, are shifted nontoxic seeds. Cells depleted sensitized Aβ42-induced death, reintroducing protective. Altogether, correlation between suggests increasing levels miRNAs brain or blocking activity could ameliorate neurodegeneration.

Language: Английский

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MicroRNAs as Potential Orchestrators of Alzheimer's Disease-Related Pathologies: Insights on Current Status and Future Possibilities

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: Oct. 12, 2021

Alzheimer's disease (AD) is a progressive and deleterious neurodegenerative disease, strongly affecting the cognitive functions memory of seniors worldwide. Around 58% affected patients live in low middle-income countries, with estimates increasing deaths caused by AD coming decade. multifactor pathology. Mitochondrial function declines brain currently emerging as hallmark this disease. It has been considered one intracellular processes severely compromised AD. Many mitochondrial parameters decline already during aging; efficiency for energy production, reactive oxygen species (ROS) metabolism de novo synthesis pyrimidines, to reach an extensive functional failure, concomitant onset conditions. Besides its impact on functions, characterized loss synapses, extracellular amyloid plaques composed amyloid-β peptide (Aβ), aggregates hyperphosphorylated Tau protein, accompanied drastic sleep disorders, sensory alterations pain sensitization. Unfortunately, till date, effective management AD-related disorders early, non-invasive diagnostic markers are yet be found. MicroRNAs (miRNAs) small non-coding nucleic acids that regulate key signaling pathway(s) various About 70% experimentally detectable miRNAs expressed where they neurite outgrowth, dendritic spine morphology, synaptic plasticity. Increasing studies suggest intimately involved specific signals formation. This pivotal considering crucial molecules studied dysfunctions increasingly acknowledged contributor via deregulating genes pathogenesis. Moreover, have proved control sensitization circadian clock system affects process. Interestingly, differential expression miRNA panels implies their potential biomarkers. In review, we will present updated analysis role regulating pathologies. We discuss current challenges against wider use future promising capabilities therapeutic means better

Language: Английский

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Lipopolysaccharides (LPSs) as Potent Neurotoxic Glycolipids in Alzheimer’s Disease (AD)

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12671 - 12671

Published: Oct. 21, 2022

Lipopolysaccharides (LPSs) are microbiome-derived glycolipids that among the most potent pro-inflammatory neurotoxins known. In Homo sapiens, major sources of LPSs gastrointestinal (GI)-tract-resident facultative anaerobic Gram-negative bacilli, including Bacteroides fragilis and Escherichia coli. have been abundantly detected in aged human brain by multiple independent research investigators, an increased abundance around within Alzheimer's disease (AD)-affected neurons has found. Microbiome-generated other endotoxins cross GI-tract biophysiological barriers into systemic circulation across blood-brain barrier brain, a pathological process increases during aging vascular disorders, 'leaky gut syndrome'. Further evidence indicates up-regulate transcription factor complex NF-kB (p50/p65) subsequently set NF-kB-sensitive microRNAs, miRNA-30b, miRNA-34a, miRNA-146a miRNA-155. These up-regulated miRNAs turn down-regulate family neurodegeneration-associated messenger RNA (mRNA) targets, mRNA encoding neuron-specific neurofilament light (NF-L) chain protein. While NF-L reported to be peripheral biofluids AD progressive lethal neurodegenerative is significantly down-regulated neocortical neurons, this may account for neuronal atrophy, loss axonal caliber alterations cell shape, modified synaptic architecture network deficits signaling capacity. This paper reviews reveals current findings on neurotoxic aspects how these contribute biological mechanism progressive, age-related ultimately disorders. recently discovered gut-microbiota-derived LPS-NF-kB-miRNA-30b-NF-L network: (i) underscores direct positive link between microbes inflammatory neuropathology, disordered cytoskeleton, disrupted synaptic-signaling stressed cells primary culture; (ii) first example glycolipid having significant detrimental miRNA-mediated actions expression NF-L, abundant filamentous protein known important maintenance homeostasis.

Language: Английский

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Stress Granules and Neurodegenerative Disorders: A Scoping Review

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: June 23, 2021

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

Language: Английский

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miR-143-3p Inhibits Aberrant Tau Phosphorylation and Amyloidogenic Processing of APP by Directly Targeting DAPK1 in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7992 - 7992

Published: July 20, 2022

The neuropathology of Alzheimer’s disease (AD) is characterized by intracellular aggregation hyperphosphorylated tau and extracellular accumulation beta-amyloid (Aβ). Death-associated protein kinase 1 (DAPK1), as a novel therapeutic target, shows promise for the treatment human AD, but regulatory mechanisms DAPK1 expression in AD remain unclear. In this study, we identified miR-143-3p promising candidate targeting DAPK1. directly bound to 3′ untranslated region mRNA inhibited its translation. decreased phosphorylation promoted neurite outgrowth microtubule assembly. Moreover, attenuated amyloid precursor (APP) reduced generation Aβ40 Aβ42. Furthermore, restoring with antagonized effects attenuating hyperphosphorylation Aβ production. addition, levels were downregulated correlated inversely hippocampus patients. Our results suggest that might play critical roles regulating both aberrant amyloidogenic processing APP thus offer potential strategy AD.

Language: Английский

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