Chronic inflammation and the hallmarks of aging

Molecular Metabolism, Год журнала: 2023, Номер 74, С. 101755 - 101755

Опубликована: Июнь 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Язык: Английский

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Metabolic reprogramming and polarization of microglia in Parkinson’s disease: Role of inflammasome and iron

Ageing Research Reviews, Год журнала: 2023, Номер 90, С. 102032 - 102032

Опубликована: Авг. 10, 2023

Язык: Английский

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Alpha Synuclein: Neurodegeneration and Inflammation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5914 - 5914

Опубликована: Март 21, 2023

Alpha-Synuclein (α-Syn) is one of the most important molecules involved in pathogenesis Parkinson’s disease and related disorders, synucleinopathies, but also several other neurodegenerative disorders with a more elusive role. This review analyzes activities α-Syn, different conformational states, monomeric, oligomeric fibrils, relation to neuronal dysfunction. The damage induced by α-Syn various conformers will be analyzed its capacity spread intracellular aggregation seeds prion-like mechanism. In view prominent role inflammation virtually all activity illustrated considering influence on glial reactivity. We others have described interaction between general cerebral dysfunctional α-Syn. Differences microglia astrocyte activation been observed when vivo presence oligomers has combined lasting peripheral inflammatory effect. reactivity was amplified, while astrocytes were damaged double stimulus, opening new perspectives for control synucleinopathies. Starting from our studies experimental models, we extended perspective find useful pointers orient future research potential therapeutic strategies disorders.

Язык: Английский

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Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Язык: Английский

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Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson’s Disease with Potential Therapeutic Implications

Biomolecules, Год журнала: 2025, Номер 15(1), С. 149 - 149

Опубликована: Янв. 19, 2025

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries recognition as chronic disease, exact pathogenesis PD remains elusive. The onset progression involve multiple complex pathological processes, with dysfunctional autophagy elevated oxidative stress serving critical contributors. Notably, emerging research has underscored interplay between in pathogenesis. Given limited efficacy therapies targeting either dysfunction or stress, it crucial to elucidate intricate mechanisms governing their develop more effective therapeutics. This review overviews role nuclear factor erythroid 2-related 2 (Nrf2), pivotal transcriptional regulator orchestrating cellular defense against these processes. By elucidating key processes PD, this will deepen our comprehensive understanding multifaceted underlying may uncover potential strategies for its prevention treatment.

Язык: Английский

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Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration

Cells, Год журнала: 2024, Номер 13(3), С. 286 - 286

Опубликована: Фев. 5, 2024

The key to the effective treatment of neurodegenerative disorders is a thorough understanding their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment glymphatic system function in neurodegeneration contributes progression pathological question arises as how related. This review highlights direct indirect influence these two seemingly independent Protein aggregates, characteristic feature neurodegeneration, correlated with clearance neuroinflammation. Glial cells cannot be overlooked when considering neuroinflammatory Astrocytes essential for functioning play crucial role inflammatory responses central nervous system. It imperative acknowledge significance AQP4, protein that exhibits high degree polarization astrocytes AQP4 influences processes have not yet been clearly delineated. Another interesting issue gut–brain axis microbiome, which potentially impact discussed A discussion correlation between may contribute exploring pathomechanism neurodegeneration.

Язык: Английский

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Targeting Neuroinflammation by Pharmacologic Downregulation of Inflammatory Pathways Is Neuroprotective in Protein Misfolding Disorders

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(7), С. 1533 - 1547

Опубликована: Март 20, 2024

Neuroinflammation plays a crucial role in the development of neurodegenerative protein misfolding disorders. This category progressive diseases includes, but is not limited to, Alzheimer's disease, Parkinson's and prion diseases. Shared pathogenesis involves accumulation misfolded proteins, chronic neuroinflammation, synaptic dysfunction, ultimately leading to irreversible neuronal loss, measurable cognitive deficits, death. Presently, there are few no effective treatments halt advancement We hypothesized that directly targeting neuroinflammation by downregulating transcription factor, NF-κB, inflammasome protein, NLRP3, would be neuroprotective. To achieve this, we used cocktail RNA therapeutics (SB_NI_112) shown brain-penetrant, nontoxic, inhibitors both NF-κB NLRP3. utilized mouse-adapted strain as model for assess aggregation glial inflammation, lifespan. Prion-diseased mice were treated either intraperitoneally or intranasally with SB_NI_112. Behavioral deficits significantly protected this combination NLRP3 downregulators. Treatment reduced against prevented spongiotic change, rescued lengthened lifespan prion-diseased mice. have identified systemic pharmacologic downregulates prevents death, slows progression Though mouse models do always predict human patient success study was due sample size number dosing methods utilized, these findings serve proof principle continued translation therapeutic SB_NI_112 disease other Based on murine model, will continue testing variety models, including disease.

Язык: Английский

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The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(14), С. 4130 - 4130

Опубликована: Июль 15, 2024

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s (PD), are severe age-related disorders with complex multifactorial causes. Recent research suggests a critical link between neurodegeneration the gut microbiome, via gut–brain communication pathway. This review examines role of trimethylamine N-oxide (TMAO), microbiota-derived metabolite, in development AD PD, investigates its interaction microRNAs (miRNAs) along this bidirectional TMAO, which is produced from dietary metabolites like choline carnitine, has been linked to increased neuroinflammation, protein misfolding, cognitive decline. In AD, elevated TMAO levels associated amyloid-beta tau pathologies, blood–brain barrier disruption, neuronal death. can cross promote aggregation amyloid proteins. Similarly, affects alpha-synuclein conformation aggregation, hallmark PD. also activates pro-inflammatory pathways NF-kB signaling, exacerbating neuroinflammation further. Moreover, modulates expression various miRNAs that involved neurodegenerative processes. Thus, microbiome–miRNA–brain axis represents newly discovered mechanistic dysbiosis neurodegeneration. MiRNAs regulate key oxidative stress, death, contributing progression. As direct consequence, specific miRNA signatures may serve potential biomarkers for early detection monitoring PD aims elucidate interrelationships microbiota, trimethylamine-N-oxide (miRNAs), central nervous system, implications these connections diseases. context, an overview current neuroradiology techniques available studying animal models used investigate intricate pathologies will be provided. summary, bulk evidence supports concept modulating pathway through changes, manipulation and/or miRNA-based therapies offer novel approaches implementing treatment debilitating neurological disorders.

Язык: Английский

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Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view

Journal of Neural Transmission, Год журнала: 2024, Номер unknown

Опубликована: Янв. 23, 2024

Abstract Fascinatingly, an abundance of recent studies has subscribed to the importance cytotoxic immune mechanisms that appear increase risk/trigger for many progressive neurodegenerative disorders, including Parkinson’s disease (PD), Alzheimer’s (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with neuroinflammatory cascades, such as ageing, immunologic dysfunction, eventually disruption blood–brain barrier “cytokine storm”, be orchestrated mainly through activation microglial cells communication neurons. The inflammatory processes prompt cellular protein dyshomeostasis. share a common feature marked by characteristic pathological hallmarks abnormal neuronal accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or case AD, they are Aβ deposits tau-containing neurofibrillary tangles. Subsequently, these further elicit neurotoxic events which contribute onset neurodegeneration its progression aggravation neuroinflammation. However, there is caveat exclusively linking neuroinflammation neurodegeneration, since it’s highly unlikely dysregulation only factor contributes manifestation disorders. It unquestionably complex interaction other factors genetics, age, environment. This endorses “multiple hit hypothesis”. Consequently, if host genetic susceptibility coupled age-related weakened system, this makes them more susceptible virus/bacteria-related infection. may trigger chronic leading dyshomeostasis accumulation, finally, lead destruction. Here, we differentiate “neuroinflammation” “inflammation” regard involvement barrier, seems intact but defect inflammation. There neuroinflammation-inflammation continuum virus-induced brain affection. Therefore, propose staging process, might developed adding blood- CSF parameters, their stage-dependent composition severeness grade. If so, suitable optimise therapeutic strategies fight beginning avoid inflammation at all.

Язык: Английский

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Biomarkers in neurodegenerative diseases: a broad overview

Exploration of Neuroprotective Therapy, Год журнала: 2024, Номер unknown, С. 119 - 147

Опубликована: Апрель 16, 2024

Degeneration and dysfunction of neurons in the brain are hallmarks neurodegenerative diseases. Over past decades, significant efforts have been devoted to development validation biomarkers for The range diversity central nervous system (CNS) diseases has continued expand, encompassing biofluid-based sources such as blood or cerebrospinal fluid (CSF), nucleic acids, tissues, imaging. While imaging tissue biopsy-based markers continually being identified their applications expanding, they do limitations compared with RNA protein biomarkers. This review comprehensively summarizes various biomarkers, including microRNA (miRNA), long noncoding (lncRNA), circulating miRNA (cimiRNA), proteins, context CNS disorders. In addition, emphasizes existing challenges associated use both clinical practice research on conclusion, this provides an insightful overview diseases, underscoring crucial role biomarker combating these debilitating conditions. article also highlights future related implementation novel trials, thereby contributing ongoing advance understanding management

Язык: Английский

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