Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167727 - 167727
Published: Feb. 1, 2025
Language: Английский
Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101755 - 101755
Published: June 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.
Language: Английский
Citations
153
Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 102032 - 102032
Published: Aug. 10, 2023
Language: Английский
Citations
61
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5914 - 5914
Published: March 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.
Language: Английский
Citations
57
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14
Published: Jan. 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.
Language: Английский
Citations
47
Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 286 - 286
Published: Feb. 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.
Language: Английский
Citations
16
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: March 7, 2025
Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.
Language: Английский
Citations
4
Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 149 - 149
Published: Jan. 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.
Language: Английский
Citations
3
Neurobiology of Disease, Journal Year: 2025, Volume and Issue: 205, P. 106791 - 106791
Published: Jan. 6, 2025
Neurodegenerative diseases (ND) are characterized by the accumulation of aggregated proteins. The glymphatic system, through its rapid exchange mechanisms between cerebrospinal fluid (CSF) and interstitial (ISF), facilitates movement metabolic substances within brain, serving functions akin to those peripheral lymphatic system. This emerging waste clearance mechanism offers a novel perspective on removal pathological in ND. article elucidates recent discoveries regarding system updates relevant concepts model. It discusses potential roles ND, including Alzheimer's disease (AD), Parkinson's (PD), multiple atrophy (MSA), proposes as therapeutic target for these conditions.
Language: Английский
Citations
2
Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(14), P. 4130 - 4130
Published: July 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.
Language: Английский
Citations
15
ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(7), P. 1533 - 1547
Published: March 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.
Language: Английский
Citations
12