Viral Infections, a Trigger and Risk Factor of Alzheimer’s Disease?

Published: Feb. 8, 2024

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed currently affected. Many causation hypotheses AD exist, yet intriguing link between viral infection its possible contribution known etiology has become an attractive focal point research for field challenging study task. In this review, we will explore historical perspective milestones that led investigate connection AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along others mentioned, include various presently considered within field. We delve into strong evidence implicating these in development also extend beyond mere associations by carefully analyzing potential mechanisms which may contribute pathology. This includes but not limited direct neuronal infections, dysregulation immune responses, impact on protein processing. Controversies challenges viral-AD relationship emerge tease out considered. Looking forward, emphasize future directions should take tackle remaining unanswered questions glaring gaps persist. Overall, review aims provide comprehensive survey past, present, infections their association development.

Language: Английский

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Neuro‐HIV—New insights into pathogenesis and emerging therapeutic targets

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(12)

Published: Nov. 9, 2023

Abstract HIV‐associated neurocognitive disorders (HAND) is a term describing complex set of cognitive impairments accompanying HIV infection. Successful antiretroviral therapy (ART) reduces the most severe forms HAND, but milder affect over 50% people living with (PLWH). Pathogenesis HAND in ART era remains unknown. A variety pathogenic factors, such as persistent replication brain reservoir, proteins released from infected cells, HIV‐induced neuroinflammation, and some components ART, have been implicated driving pathogenesis ART‐treated individuals. Here, we propose another factor—impairment cholesterol homeostasis lipid rafts by HIV‐1 protein Nef—as possible contributor to pathogenesis. These effects Nef on may also underlie other factors that constitute multifactorial nature The proposed Nef‐ cholesterol‐focused mechanism provide long‐sought unified explanation takes into account all contributing factors. Evidence for impairment cellular balance, potential this opportunities therapeutically target element are discussed.

Language: Английский

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ACH2.0/E, the Consolidated Theory of Conventional and Unconventional Alzheimer’s Disease: Origins, Progression, and Therapeutic Strategies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6036 - 6036

Published: May 30, 2024

The centrality of amyloid-beta (Aβ) is an indisputable tenet Alzheimer's disease (AD). It was initially indicated by the detection (1991) a mutation within Aβ protein precursor (AβPP) segregating with disease, which served as basis for long-standing Amyloid Cascade Hypothesis (ACH) theory AD. In intervening three decades, this notion affirmed and substantiated discovery numerous AD-causing AD-protective mutations all, without exception, affecting structure, production, intraneuronal degradation Aβ. ACH postulated that caused driven extracellular When it became clear not case, largely discredited, new AD, dubbed ACH2.0 to re-emphasize Aβ, formulated. ACH2.0, AD physiologically accumulated (iAβ) derived from AβPP. Upon reaching critical threshold, triggers activation autonomous AβPP-independent iAβ generation pathway; its output retained intraneuronally drives pathology. bridge between AβPP generated independently neuronal integrated stress response (ISR) elicited former. ISR severely suppresses cellular synthesis; concurrently, activates production small subset proteins, apparently includes components necessary operation pathway are absent under regular circumstances. above sequence events defines "conventional" both differentially iAβ. Since can be multitude stressors, logic mandates another class referred "unconventional", has occur. Unconventional defined where stressor distinct AβPP-derived elicits ISR. Thus, essence both, conventional unconventional, forms one same, namely autonomous, self-sustainable, What distinguishes them manner pathway, i.e., mode causation disease. unconventional processes occurring at locations distant seemingly unrelated brain as, say, knee potentially trigger present study asserts these include traumatic injury (TBI), chronic encephalopathy, viral bacterial infections, wide array inflammatory conditions. considers pathways common all occurrences culminate in elicitation ISR, analyzes dynamics versus shows how former morph into latter, explains single TBI hasten occurrence why takes multiple TBIs proposes appropriate therapeutic strategies. posits yet may occur initiated ISR-unrelated activator, consolidates notions designated ACH2.0/E (for expanded ACH2.0), incorporates special case retains produced driving agent

Language: Английский

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Immune receptors and aging brain

Bioscience Reports, Journal Year: 2024, Volume and Issue: 44(2)

Published: Feb. 1, 2024

Abstract Aging brings about a myriad of degenerative processes throughout the body. A decrease in cognitive abilities is one hallmark phenotypes aging, underpinned by neuroinflammation and neurodegeneration occurring brain. This review focuses on role different immune receptors expressed cells central peripheral nervous systems. We will discuss how brain act as sentinels effectors age-dependent shift ligand composition. Within this ‘old-age-ligand soup,’ some contribute directly to excessive synaptic weakening from within neuronal compartment, while others amplify damaging inflammatory environment Ultimately, chronic inflammation sets up positive feedback loop that increases impact ligand–receptor interactions brain, leading permanent loss.

Language: Английский

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Changes in the Expression of Proteins Associated with Neurodegeneration in the Brains of Mice after Infection with Influenza A Virus with Wild Type and Truncated NS1

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2460 - 2460

Published: Feb. 20, 2024

Influenza type A virus (IAV) infection is a major cause of morbidity and mortality during influenza epidemics. Recently, specific link between IAV neurodegenerative disease progression has been established. The non-structural NS1 protein regulates viral replication antagonizes host antiviral responses, contributing to virulence. In the present study, we have prepared mouse lung-to-lung adapted NS1-truncated (NS80ad). Transcriptome analysis gene expression in lungs revealed that with wild-type A/WSN/33 (WSN), NS80, NS80ad viruses resulted different regulation genes involved signaling pathways associated cell proliferation, inflammatory response, development diseases. did not influence RIG-I-like receptor pathway brains. Lethal IAVs dysregulated proteins diseases (CX3CL1/Fractalkine, Coagulation factor III, CD105/Endoglin, CD54/ICAM-1, insulin-like growth factor-binding (IGFBP)-2, IGFBP-5, IGFBP-6, chitinase 3-like 1 (CHI3L1), Myeloperoxidase (MPO), Osteopontin (OPN), cystatin C, LDL R). Transcription GATA3 mRNA was decreased, MPO inhibited brain infected NS80 viruses. addition, truncation led reduced IGFBP-2, CHI3L1, MPO, LDL-R Our results indicate influences function, this might occur mostly through protein. These findings suggest abovementioned represent promising target for potentially effective immunotherapy against neurodegeneration.

Language: Английский

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