Synergistic Action of Vitamin D3 and A Protects Motor Activity by Regulating Reactive Astrocytes, Inflammatory Cytokines, and Dopaminergic Activity in the Corticobasal Loop of a Mice Model of Extrapyramidal Syndrome DOI Creative Commons
Mujittapha U. Sirajo,

Yahya K. Maigari,

Abdulrashid Sunusi

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 20, 2023

Abstract Background: Extrapyramidal syndromes (EPS) represent neurological side effects of antipsychotic medications, characterized by motor disturbances. While previous studies have indicated the neuroprotective vitamin D and A against EPS, underlying mechanisms this protection remain unclear. Methods: Twenty-four adult male mice were categorized into four groups: positive negative control groups, one receiving a dopamine antagonist, other both antagonist vitamins A. Sections corticobasal loop, specifically cortex (M1) basal nuclei (CPu), prepared for Immunohistochemistry (IHC) stained with Glial Fibrillary Acidic Protein (GFAP) to visualize active astrocytes. ELISA assays TNF-α, IL-6, IL-4, IL-13, levels performed on homogenized brain sections. Results: The EPS group exhibited significant increase in TNF-α IL-6 M1 CPu. Treatment agonists D/A resulted reductions levels. Only Vitamin showed decline TNF-α. recorded decreases IL-4 IL-13 significantly elevated agonist groups. was notably increased Dopamine concentration declined group, improvements observed groups treated agonists, D, Reactive astrocytes expressed CPu but poorly regions. Conclusions: is linked astrocyte activation, an upsurge pro-inflammatory cytokines, anti-inflammatory loop. Administration D3 found exert its suppressing cytokines repressing associated activation.

Language: Английский

Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review DOI Open Access
Paulina Iwaniak,

Maja Owe-Larsson,

Ewa M. Urbańska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2915 - 2915

Published: March 2, 2024

In the era of a steadily increasing lifespan, neurodegenerative diseases among elderly present significant therapeutic and socio-economic challenge. A properly balanced diet microbiome diversity have been receiving attention as targets for interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival death, gut dysbiosis was identified Parkinson’s disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota hosts numerous compounds with immune- neuromodulating properties. This broad narrative review presents data supporting concept that microbiota, Trp-kynurenine (KYN) pathway aryl hydrocarbon receptors (AhRs) form triad involved PD. disturbed gut–brain axis allows bidirectional spread pro-inflammatory molecules α-synuclein, which contribute to development/progression disease. We suggest peripheral levels kynurenines AhR ligands are strongly linked Trp metabolism should be studied together composition microbiota. Such approach can clearly delineate sub-populations PD patients manifesting microbiota–Trp-KYN–brain triad, who would benefit from modifications metabolism. Analyses microbiome, Trp-KYN metabolites signaling shed light on mechanisms intestinal distress identify new diagnosis treatment early-stage Therapeutic based combination well-defined food regimen, probiotics seem potential require further experimental clinical research.

Language: Английский

Citations

11
Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets DOI
Fernanda V. Carvalho,

Harold E. Landis,

Bruk Getachew

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 105 - 132

Published: Jan. 1, 2024

Language: Английский

Citations

9
Inflammaging and Brain Aging DOI Open Access
Maria Carolina Jurcău, Anamaria Jurcău,

Alexander Cristian

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10535 - 10535

Published: Sept. 30, 2024

Progress made by the medical community in increasing lifespans comes with costs of incidence and prevalence age-related diseases, neurodegenerative ones included. Aging is associated a series morphological changes at tissue cellular levels brain, as well impairments signaling pathways gene transcription, which lead to synaptic dysfunction cognitive decline. Although we are not able pinpoint exact differences between healthy aging neurodegeneration, research increasingly highlights involvement neuroinflammation chronic systemic inflammation (inflammaging) development age-associated via pathogenic cascades, triggered dysfunctions circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender susceptibility course neurodegeneration that appear be mediated glial cells emphasize need for future this area an individualized therapeutic approach. rejuvenation still its very early infancy, accumulated knowledge on various involved promoting senescence opens perspective interfering these preventing delaying senescence.

Language: Английский

Citations

6
Lung-specific SFTPC mutations lead to neurodevelopmental disorders with neuroinflammation DOI
Hanmin Dong,

Congwen Zang,

Lili Liu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 753, P. 151479 - 151479

Published: Feb. 11, 2025

Language: Английский

Citations

0
Exploring Parkinson’s Disease-Associated Depression: Role of Inflammation on the Noradrenergic and Serotonergic Pathways DOI Creative Commons
Tuane Bazanella Sampaio, Marissa Giovanna Schamne, Jean Rodrigo Santos

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(1), P. 100 - 100

Published: Jan. 20, 2024

Parkinson’s disease (PD) is a multifactorial disease, with genetic and environmental factors contributing to the onset. Classically, PD movement disorder characterized by loss of dopaminergic neurons in nigrostriatal pathway intraneuronal aggregates mainly constituted protein α-synuclein. However, patients also display non-motor symptoms, including depression, which have been linked functional abnormalities non-dopaminergic neurons, serotonergic noradrenergic ones. Thus, through this comprehensive literature review, we shed light on impairment depression PD, focusing putative involvement inflammatory mechanisms.

Language: Английский

Citations

4
Ginsenosides Rg1, Rb1 and rare ginsenosides: promising candidate agents for Parkinson's disease and Alzheimer's disease and network pharmacology analysis DOI Creative Commons

Mingchun Jiang,

Jiaxin Chi,

Yifan Qiao

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107578 - 107578

Published: Jan. 5, 2025

Ginseng has been commonly used as a traditional Chinese medicine in Asian countries for thousands of years. Ginsenosides are the main pharmacologically active ingredients isolated from ginseng and have neuroprotective effects treatment neurodegenerative disorders, such Parkinson's disease (PD) Alzheimer's (AD). To summarise investigate protective roles ginsenosides their underlying mechanisms PD AD, we ''Ginsenoside", ''Parkinson's disease", ''Alzheimer's ''anti-inflammatory", ''antioxidant", ''apoptosis" keywords to search extract relevant literature information scientific databases Elsevier, PubMed, Google Scholar databases. In particular, network pharmacology identify potential targets Rg1 Rb1 AD. By analysing existing research advances results, found that ginsenosides, primarily mediated through anti-inflammation, anti-apoptosis anti-oxidative stress, etc, may be associated with PI3K/Akt, BDNF/TrkB, MAPKs, NF-κB, Nrf2 Wnt/β-catenin signalling pathways. This review systematically summarises different Rg1, Rb1, rare AD provides new strategies disorders. Network paradigm using Rb1.

Language: Английский

Citations

0
Dynamics of retinal changes in early-stage Parkinson’s disease DOI Creative Commons
Ane Murueta‐Goyena, Sara Teijeira‐Portas,

Elisa Blanco Martín

et al.

Acta Neuropathologica Communications, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 31, 2025

Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by motor symptoms, with emerging evidence suggesting retinal pathology, particularly in the ganglion cell-inner plexiform layer (GCIPL), detectable via optical coherence tomography (OCT). This study aimed to characterize early dynamics PD using OCT. We conducted prospective one-year longitudinal multicenter involving 53 early-stage patients duration of 5 years or less and 52 controls. The participants underwent spectral-domain OCT, primary visual function cognitive examinations. examined baseline measures short-term differences between groups linear mixed effects models. In patients, GCIPL thickness central regions was increased up 4 μm, rate thinning parafoveal - 0.61 [0.29] µm/year faster over follow-up period than controls 2- 3-mm ring (p = 0.039). greater associated poorer contrast sensitivity reduced performance on Farnsworth D15 color vision test. It also predicted subsequent both (2- ring) inner nuclear 5-mm rings). However, this not linked prevalent progressive manifestations. conclusion, provides first detailed topographical description revealing accelerated PD. macular region shows complex variable among but these changes precede progression clinical scales.

Language: Английский

Citations

0
Frequencies of Circulating Immune Cells in Patients with Parkinson’s Disease: Correlation with MDS-UPDRS Scores DOI Creative Commons
David Goldeck,

Lilly Oettinger,

Tamàs Fülöp

et al.

Journal of Integrative Neuroscience, Journal Year: 2025, Volume and Issue: 24(2)

Published: Feb. 21, 2025

Background: Parkinson’s Disease (PD) is associated with dysregulated/chronic inflammation. The immune system has multiple roles including beneficial effects such as clearing alpha synuclein aggregates. However, peripheral cells entering the brain may also contribute to inflammation and neurodegeneration. To identify which might have a negative impact could be potential therapeutic targets, we compared signatures of patients healthy controls. Methods: Multicolor flow cytometry was used determine frequencies major cell subsets in blood mononuclear (PBMCs) PD Because Cytomegalovirus (CMV) infection on distribution subsets, particularly cluster differentiation (CD)8+ T-cells, all participants were tested for CMV seropositivity. Results: Although cohort 35 exhibited well-established T-cell signature driven by infection, there no differences differentiated or pro-inflammatory B-cells natural killer (NK-cells) attributable disease. percentages myeloid-derived suppressor (MDSCs) higher than Moreover, CD14+CD16+ (intermediate) monocytes expressing C-C chemokine receptor type 5 (CCR5) correlated disease severity assessed Movement Disorder Society’s revised version Unified Rating Scale (MDS-UPDRS) score duration. Conclusions: A comprehensive evaluation circulating revealed myeloid between controls some correlation monocyte abundance severity.

Language: Английский

Citations

0
Exercise, Neuroprotective Exerkines, and Parkinson’s Disease: A Narrative Review DOI Creative Commons

Alexandra K. Mitchell,

Rebecca R. Bliss,

Frank Church

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1241 - 1241

Published: Sept. 30, 2024

Parkinson's disease (PD) is a prevalent neurodegenerative in which treatment often includes an exercise regimen. Exercise neuroprotective animal models of PD, and, more recently, human clinical studies have verified exercise's disease-modifying effect. Aerobic and resistance training improve many PD's motor non-motor symptoms, while neuromotor therapy stretching/flexibility exercises positively contribute to the quality life people with PD. Therefore, understanding role managing this complex disorder crucial. Exerkines are bioactive substances that synthesized released during been implicated several positive health outcomes, including neuroprotection. protect neuronal cells vitro rodent PD vivo. both increase exerkine levels blood, suggesting for exerkines theory. Many demonstrate potential protecting brain against pathological missteps caused by Every person (people) (PwP) needs comprehensive plan tailored their unique abilities. Here, we provide template help PwP understand importance treating describe barriers confronting attempt exercise, suggestions overcoming these barriers, explore In conclusion, together create powerful system should slowing chronic progression

Language: Английский

Citations

3
The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies DOI Creative Commons
Vharoon Sharma Nunkoo,

Alexander Cristian,

Anamaria Jurcău

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2540 - 2540

Published: Nov. 7, 2024

The impressive achievements made in the last century extending lifespan have led to a significant growth rate of elderly individuals populations across world and an exponential increase incidence age-related conditions such as cardiovascular diseases, diabetes mellitus type 2, neurodegenerative diseases. To date, geroscientists identified 12 hallmarks aging (genomic instability, telomere attrition, epigenetic alterations, loss proteostasis, impaired macroautophagy, mitochondrial dysfunction, nutrient sensing, cellular senescence, stem cell exhaustion, defective intercellular communication, chronic inflammation, gut dysbiosis), intricately linked among each other, which can be targeted with senolytic or senomorphic drugs, well more aggressive approaches cell-based therapies. side effects seriously limit use these drugs. However, since rejuvenation is dream mankind, future research expected improve tolerability available drugs highlight novel strategies. In meantime, medical community, healthcare providers, society should decide when start treatments how tailor them individually.

Language: Английский

Citations

3