The Role of Labile Iron on Brain Proteostasis; Could it be an Early Event of Neurodegenerative Disease? DOI Open Access

Aiyarin Kittilukkana,

Jannarong Intakhat,

Chalermchai Pilapong

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

Abstract Iron deposits in the brain are a natural consequence of aging. accumulation, especially form labile iron, can trigger cascade adverse effects, eventually leading to neurodegeneration and cognitive decline. Aging also increases dysfunction cellular proteostasis. The question whether iron alters proteostasis is now being pondered. Herein, we investigated effect ferric citrate, considered as on various aspects neuronal cell lines, established an animal model having diet order evaluate alteration along with behavioral effects. According vitro study, was found activate lysosome formation but inhibits lysosomal clearance function. Furthermore, presence alter autophagic flux induce accumulation protein aggregates. RNA-sequencing analysis further reveals upregulation terms related neurodegenerative disease-related terms. vivo iron-rich does not overload conditions detrimental behavior male Wistar rats. However, promote region-dependent manner, particularly cortex. By staining for markers misfolding proteins cerebral cortex, actually autophagy proteins. These findings emphasize importance proteostasis, which could be implicated developing neurological diseases. Graphical abstract

Language: Английский

Analysis of α-syn and parkin interaction in mediating neuronal death in Drosophila model of Parkinson's disease DOI Creative Commons
Sonia Narwal, Amit Singh, Meghana Tare

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 4, 2024

One of the hallmarks Parkinson's Disease (PD) is aggregation incorrectly folded α-synuclein (SNCA) protein resulting in selective death dopaminergic neurons. Another form PD characterized by loss-of-function an E3-ubiquitin ligase, parkin. Mutations SNCA and parkin result impaired mitochondrial morphology, causing loss Despite extensive research on individual effects parkin, their interactions neurons remain understudied. Here we employ Drosophila model to study effect collective overexpression along with downregulation posterior brain. We found that causes a reduction number neuronal clusters region adult brain, which manifested as progressive locomotor dysfunction. Overexpression collectively results altered morphology cluster-specific manner, only subset Further, transcriptional However, this not further enhanced upon downregulation. This suggests may be additive. Our thus provides insights into potential link between interactions. These manner for over time, unraveling molecular involved etiology Disease.

Language: Английский

Citations

4
Epigenetic regulation of iron metabolism and ferroptosis in Parkinson’s disease: Identifying novel epigenetic targets DOI

Xiaodie Gao,

Jun Ding, Junxia Xie

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Language: Английский

Citations

0
Lactoferrin as a Candidate Multifunctional Therapeutic in Synucleinopathies DOI Creative Commons
Caroline A. Barros, Tuane C. R. G. Vieira

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 380 - 380

Published: April 6, 2025

Lactoferrin (Lf) is a multifunctional glycoprotein with well-established antimicrobial, anti-inflammatory, and iron-binding properties. Emerging evidence suggests that Lf also plays neuroprotective role, particularly in neurodegenerative disorders characterized by protein aggregation, such as Parkinson's disease (PD). Alpha-synuclein (aSyn) aggregation pathological hallmark of PD other synucleinopathies, contributing to neuronal dysfunction progression. Recent studies indicate may interfere aSyn iron chelation, modulation oxidative stress neuroinflammation. Additionally, Lf's ability cross the blood-brain barrier its potential impact on gut-brain axis highlight promise therapeutic agent. This review explores mechanisms action disease-modifying therapy, innovative delivery strategies could enhance clinical applicability. By addressing dimensions we propose compelling candidate for future research development diseases.

Language: Английский

Citations

0
Enhancing drug administration in Drosophila melanogaster : a method for using solid dispersions for improved solubility and bioavailability DOI Creative Commons
Sunayn Cheku, Blase Rokusek, Mahesh Pattabiraman

et al.

Fly, Journal Year: 2025, Volume and Issue: 19(1)

Published: April 25, 2025

Drosophila melanogaster is a widely used model organism for diseases such as Parkinson's disease, Alzheimer's obesity, and diabetes. However, compound administration-based toxicological behavioural studies on have been hindered by technical difficulties associated with inefficient administration of hydrophobic compounds. This study illustrates general method to make distribute PEG 8000-based solid dispersions three compounds, distearoylglycerol (DSG) geldanamycin (GA) RU486 D. melanogaster. The were validated, in vitro, using nuclear magnetic resonance spectroscopy (NMR), higher aqueous solubility. also describes different methods administer the dispersions: subcutaneous injections, mixing food, capillary feeder assay (CAFE). We show that presence 1% DMSO decreases survival, whereas does not an adverse effect. Lastly, we showed prepared PEG-RU486 formulation signs enhanced bioavailability when compared dissolved ethanol. methodology described provides easy effective means compounds CAFE assay, or it food.

Language: Английский

Citations

0
Senolytic and senomorphic secondary metabolites as therapeutic agents in Drosophila melanogaster models of Parkinson’s disease DOI Creative Commons

Sean Miller,

Rayyan Y. Darji,

Sami Walaieh

et al.

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 28, 2023

Drosophila melanogaster is a valuable model organism for wide range of biological exploration. The well-known advantages D. include its relatively simple biology, the ease with which it genetically modified, low financial and time costs associated their short gestation life cycles, large number offspring they produce per generation. has facilitated discovery many significant insights into pathology Parkinson’s disease (PD) served as an excellent preclinical PD-related therapeutic discovery. In this review, we provide overview major models PD, each unique PD-relevant targets. These are discussed in context past, current, future potential use studying utility secondary metabolites agents PD. Over last decade, senolytics have garnered exponential interest ability to mitigate broad spectrum diseases, including Therefore, emphasis placed on senolytic senomorphic properties metabolites. It expected that will continue be critical effort understand improve treatment involvement translational studies focused

Language: Английский

Citations

4
Syagrus coronata fixed oil prevents rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster DOI
Ricardo Gomes dos Santos Nunes, Luciclaudio Cassimiro de Amorim, Iverson Conrado Bezerra

et al.

Journal of Toxicology and Environmental Health, Journal Year: 2024, Volume and Issue: 87(12), P. 497 - 515

Published: April 15, 2024

One prominent aspect of Parkinson's disease (PD) is the presence elevated levels free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim this investigation was examine potential neuroprotective effects S. fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young specimens (3–4 d old) were exposed diet supplemented with rotenone (50 µM) for 7 without inclusion (0.2 mg/g diet). Data demonstrated that exposure resulted in significant locomotor impairment increased mortality rates flies. Further, administration reduced total thiol but lipid peroxidation, iron (Fe) levels, nitric oxide (NO) while decreasing capacity mitochondria. Concomitant exhibited protective effect rotenone, as evidenced by return control Fe, NO, thiols, lowered peroxidation reversed impairment, enhanced % cell viability. Molecular docking lipidic components enzymes showed strong binding affinity superoxide dismutase (SOD) glutathione peroxidase (GPX1) enzymes. Overall, treatment found prevent movement disorders oxidative stress

Language: Английский

Citations

1
The role of labile iron on brain proteostasis; could it be an early event of neurodegenerative disease? DOI

Aiyarin Kittilukkana,

Jannarong Intakhad,

Chalermchai Pilapong

et al.

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 756, P. 110020 - 110020

Published: April 30, 2024

Language: Английский

Citations

1
PAK6 promotes neuronal autophagy by regulating TFEB nuclear translocation. DOI Creative Commons
Francesco Agostini,

Rossella Agostinis,

Martina Di Rocco

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 5, 2024

Autophagy is a highly conserved homeostatic process essential for the bulk degradation of cytoplasmic components and aggregated proteins. Multiple evidence indicates that impairment (macro)autophagy leads to neurodegeneration, such as Parkinson disease (PD). Our previous work showed p21 activated kinase 6 (PAK6) interacts with PD-associated leucine-rich repeat (LRRK2) promote neurite outgrowth in mouse striatum; still function PAK6 brain largely unknown. Here, we found downregulation neuronal but not glial mbt , D. melanogaster homolog PAK6, impairs autophagy-lysosomal function. overexpression cells C. elegans increases transcription factor EB (TFEB) nuclear translocation activity-dependent manner. Mechanistically, forms complex TFEB regulate its localization manner dependent on phosphorylation binding 14-3-3 proteins at S467. In line ability autophagy, exacerbates alpha-synuclein toxicity Drosophila dopaminergic neurons. Moreover, substantia nigra mutant LRRK2 mice reduces burden phosphorylated Altogether, our study uncovers novel role positive regulator autophagy via suggests modulating activity may represent way selectively turn neurons, implications treatment neurodegenerative disorders.

Language: Английский

Citations

0
The Underestimated Role of Iron in Frontotemporal Dementia: A Narrative Review DOI Open Access

Sara Ferretti,

Isabella Zanella

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12987 - 12987

Published: Dec. 3, 2024

The term frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders characterized by the progressive degeneration frontal and temporal lobes brain with language impairment changes in cognitive, behavioral executive functions, some cases motor manifestations. A high proportion FTD are due to genetic mutations inherited an autosomal-dominant manner variable penetrance depending on implicated gene. Iron is crucial microelement that involved several cellular essential functions whole body plays additional specialized roles central nervous system (CNS) mainly through its redox-cycling properties. Such feature may be harmful under aerobic conditions, since it lead generation highly reactive hydroxyl radicals. Dysfunctions iron homeostasis CNS indeed disorders, although still challenging determine whether dyshomeostasis this but metal direct cause neurodegeneration, contributor factor or simply consequence other mechanisms. Unlike many evidence dysfunction scarce; nonetheless, recent literature intriguingly suggests possible involvement. present review aims summarize what currently known about contribution based clinical, imaging, histological, biochemical molecular studies, further suggesting new perspectives offering insights for future investigations underexplored field research.

Language: Английский

Citations

0
Effect of Soybean and Seaweed-based Diets on Growth Performance, Feed Utilization, and Gut Microbiota of Tilapia: A Systematic Review and Meta-analysis DOI Creative Commons
Leonildo dos Anjo Viagem, Jean N. Hakizimana, Cyrus Rumisha

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 24, 2023

Abstract Tilapia, a significant aquaculture species globally, relies heavily on feed for its production. While numerous studies have investigated the impact of soybean and seaweed-based diets tilapia, comprehensive understanding remains elusive. This review aimed at evaluating synthesizing existing literature these diets’ effects, focusing growth performance, utilization, gut microbiota. A systematic search databases was conducted using Preferred Reporting Items Systematic Reviews Meta-Analyses (PRISMA) guidelines total 57 were included in qualitative analysis 24 meta-analysis. The results indicated that soybean-based diets, 59.4% inclusion level improved Specific Growth Rate (SGR) tilapia with an effect size -2.14 (95% CI: -2.92, -1.37; p < 0.00001; I 2 = 99%) did not improve conversion rate (FCR), as 1.80 0.72, 2.89; 0.001; 100%). For 15,9% SGR, -0.74 -1.70, 0.22; 0.13; 99%), FCR -0.70 -1.94, 0.54; 0.27; Regarding microbiota, noted lack meeting criteria tilapia. However, findings from other farmed fishes suggested could diverse effects microbiota composition promote beneficial study suggests incorporating can SGR Seaweed-based while demonstrating improvement analyzed parameters 15.9%, potential to contribute sustainability industry when incorporated lower levels.

Language: Английский

Citations

0