Elucidating the Biochemical Role of Novel Enzyme Targets in Neurodegenerative Disorders DOI Creative Commons

Abdullah Abbas Hamzah Al-Rubaye

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

Published: Oct. 19, 2023

Abstract Introduction: Neurodegenerative disorders, characterized by progressive neuronal loss, remain a significant clinical challenge due to their multifactorial etiology. While numerous enzymes have been implicated in pathogenesis, there remains knowledge gap regarding the precise biochemical roles of several novel enzyme targets. Methods: This study encompassed multi-pronged approach, involving patient-derived samples from Alzheimer's and Parkinson's cases (n=156), an ALS mouse model (n=50), CRISPR-Cas9 edited Huntington's Disease zebrafish (n=100). Enzyme activity assays, localization microscopy, interaction pathway analyses were conducted. Results: Elevated Aminotransferases was observed 78% compared controls (p<0.05). The revealed 30% reduction motor neuron counts tandem with altered (p<0.01). successfully displayed genetic markers post-CRISPR editing, indicating 95% editing efficiency. Furthermore, interactions between established neurodegenerative pathways identified. Conclusion: Mine findings highlight pivotal role targets offering potential avenues for early detection therapeutic interventions. intricate interplay these known disease underscores need integrated approach understand mechanisms holistically.

Language: Английский

Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in mice DOI Creative Commons

Mansi Dahalia,

Sparsh Gupta, Haya Majid

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 22, 2025

Background Epilepsy is a neurological disorder characterized by recurrent seizures due to abnormal electrical activity in the brain. Pirfenidone, an antifibrotic drug, has shown anti-inflammatory and antioxidant properties various disease models, including conditions. However, its potential anticonvulsant effects have not been thoroughly explored. This study aims evaluate of pirfenidone pentylenetetrazol-induced kindling model epilepsy, focusing on effect seizure activity, cognition, profiles, inflammatory markers, neurotransmitter balance, liver enzyme levels, histopathological changes. Methods Healthy male Swiss albino mice were subjected acute Increasing Current Electroshock test chronic pentylenetetrazol-kindling model. Pirfenidone was administered at doses 100, 200, 300 mg/kg, orally, with sodium valproate as standard drug. Seizure severity cognitive function assessed model, along biochemical assays that evaluated enzymes, levels. Histopathological changes also hippocampus cortex experimental mice. Results 200 mg/kg significantly increased Threshold test, indicating protective against seizures. In delayed onset reduced severity, dose showing strongest impact. demonstrated significant improvements function, evidenced enhanced performance passive avoidance elevated plus maze tests. Antioxidant profiles showed levels superoxide dismutase, catalase, glutathione, corresponding reduction malondialdehyde acetylcholinesterase pro-inflammatory cytokines interleukin-6, interleukin-1β, transforming growth factor-β, tumor necrosis factor- α, high-mobility group box-1, toll-like receptor-4, gamma-aminobutyric acid, decreased glutamate modulated aspartate aminotransferase alanine analysis revealed ameliorated cellular disintegration neuronal damage cortex. Conclusion shows anticonvulsant, anti-inflammatory, hepatoprotective, neuroprotective agent, additional benefits improving cognition oxidative stress epilepsy treatment. Further studies are required explore long-term safety efficacy.

Language: Английский

Citations

2
Sodium butyrate ameliorates mitochondrial oxidative stress and alterations in membrane-bound enzyme activities in pentylenetetrazole-induced kindling rat model DOI
Olusegun L. Adebayo,

Gbemileke Emmanuel Luro,

Ifewunmi Deborah Akeju

et al.

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(2)

Published: Feb. 6, 2025

Language: Английский

Citations

1
Brain targeted lactoferrin coated lipid nanocapsules for the combined effects of apocynin and lavender essential oil in PTZ induced seizures DOI Creative Commons
Julie R. Youssef, Nabila Boraie, Fatma Ahmed Ismail

et al.

Drug Delivery and Translational Research, Journal Year: 2024, Volume and Issue: 15(2), P. 534 - 555

Published: May 31, 2024

Apocynin (APO) is a plant derived antioxidant exerting specific NADPH oxidase inhibitory action substantiating its neuroprotective effects in various CNS disorders, including epilepsy. Due to rapid elimination and poor bioavailability, treatment with APO challenging. Correspondingly, novel APO-loaded lipid nanocapsules (APO-LNC) were formulated coated lactoferrin (LF-APO-LNC) improve br ain targetability prolong residence time. Lavender oil (LAV) was incorporated into LNC as bioactive ingredient act synergistically alleviating pentylenetetrazol (PTZ)-induced seizures. The optimized LF-APO-LAV/LNC showed particle size 59.7 ± 4.5 nm narrow distribution 6.07 1.6mV zeta potential) high entrapment efficiency 92 2.4% sustained release (35% 72 h). Following subcutaneous administration, brought about ⁓twofold increase plasma AUC MRT compared APO. A Log BB value of 0.2 0.14 at 90 min reflects increased brain accumulation. In PTZ-induced seizures rat model, Modified Racine score 0.67 0.47 significant latency decrease duration. Moreover, oxidant/antioxidant capacity inflammatory markers levels tissue significantly improved. Histopathological immunohistochemical assessment sections further supported these findings. results suggest APO/LAV combination LF-coated promising approach counteract

Language: Английский

Citations

4
Effect of solid lipid nanoparticles loaded with valproate and metformin on pentylenetetrazole-induced epilepsy in rats DOI

R. Abinaya,

V. K. Kalaichelvan,

K. Gopalasatheeskumar

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

Citations

0
Vitamin E-Valproate Co-Therapy Attenuated oxidative stress, neuroinflammation, related cognitive deficits and neuronal damage in Cypermethrin exacerbated seizure DOI
Aminu Imam, A. M. Tunde, Abdulbasit Amin

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract Background: Epilepsy, characterized by recurrent seizures and associated cognitive impairments, is often exacerbated environmental neurotoxins such as Cypermethrin. This study investigates the effects of Cypermethrin (CPM) on Pentylenetetrazole (PTZ)-induced potential neuroprotective properties Vitamin E (VIT E) valproate (VAP), both alone in combination. Methods: Behavioral tests, biochemical assays, immunohistochemical analyses were conducted to assess seizure severity, performance, neuronal integrity, markers neuroinflammation oxidative stress. Results: PTZ-induced significantly increased severity impaired performance T-maze, Y-maze, Morris’ water maze with these deficits being CPM. Immunohistochemical staining revealed substantial interneuron loss hippocampus, accompanied heightened microglial activation. Biochemical showed elevated levels pro-inflammatory cytokines (TNF-α) stress (MDA), alongside reduced antioxidant enzyme activity (SOD). Therapeutic intervention VAP or VIT mitigated varying degrees. Combination therapy was particularly effective, demonstrating significant improvements scores, reductions markers. These findings underscore synergistic benefits combining managing neuropathologies. Conclusion: This highlights exacerbating toxins seizure-related impairments while providing evidence for antioxidant-based combination therapies a promising approach mitigate effects.

Language: Английский

Citations

0
Scorpion venom heat-resistant synthesized peptide ameliorates epileptic seizures and imparts neuroprotection in rats mediated by NMDA receptors DOI
Ao‐Ran Sui, Hua Piao,

Si-Ting Xiong

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 978, P. 176704 - 176704

Published: June 1, 2024

Language: Английский

Citations

2
Diverse perspectives in zebrafish seizure models: An exploration of chemical inducers DOI Creative Commons
Husnul Khotimah, Fathina Zahrani Rahmaniar,

Fatimah Az Zahra

et al.

World Journal of Advanced Research and Reviews, Journal Year: 2024, Volume and Issue: 21(3), P. 865 - 877

Published: March 12, 2024

Numerous studies have investigated seizures in zebrafish, employing diverse methods to induce and observe epilepsy. Chemical inducers become indispensable tools for precisely manipulating neural activity controlled experiments. This research is dedicated a meticulous comparison analysis of various seizure-inducing chemicals zebrafish. The selected chemical include pentylenetetrazole (PTZ), kainic acid (KA), picrotoxin (PTX), pilocarpine, other substances. primary mechanism these involves altering neurotransmitter receptors, particularly GABA glutamate, at inhibitory or excitatory synapses. alteration creates an imbalance between signals the brain, contributing epileptogenesis. resulting hyperactivity zebrafish brain disrupts metabolism, elevates reactive oxygen species (ROS), causes neuronal damage. induction offers valuable insights into neurological enabling observation behaviors such as whole-body contractions, loss posture, freezing. Various parameters can be adjusted examine effects on development replicate types seizures, status epilepticus temporal lobe Despite array options available, many remain underutilized studies. To ensure successful models, monitoring gene expression markers c-fos, which represents activity, becomes crucial. Additionally, scoring system employed analyze seizure severity identify treatment efficacy. existing gaps utilizing present great opportunities future model development. chemically-induced pivotal unraveling mechanisms, significantly advancements research.

Language: Английский

Citations

0
Studying the Anti-Anxiety and Anti-Convulsant Impacts of Royal Jelly in Mice DOI
Sarah Wolfensohn, Penny Hawkins, Elliot Lilley

et al.

International Journal of Pharmaceutical and Phytopharmacological Research, Journal Year: 2024, Volume and Issue: 14(5), P. 25 - 30

Published: Jan. 1, 2024

Language: Английский

Citations

0
Elucidating the Biochemical Role of Novel Enzyme Targets in Neurodegenerative Disorders DOI Creative Commons

Abdullah Abbas Hamzah Al-Rubaye

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

Published: Oct. 19, 2023

Abstract Introduction: Neurodegenerative disorders, characterized by progressive neuronal loss, remain a significant clinical challenge due to their multifactorial etiology. While numerous enzymes have been implicated in pathogenesis, there remains knowledge gap regarding the precise biochemical roles of several novel enzyme targets. Methods: This study encompassed multi-pronged approach, involving patient-derived samples from Alzheimer's and Parkinson's cases (n=156), an ALS mouse model (n=50), CRISPR-Cas9 edited Huntington's Disease zebrafish (n=100). Enzyme activity assays, localization microscopy, interaction pathway analyses were conducted. Results: Elevated Aminotransferases was observed 78% compared controls (p<0.05). The revealed 30% reduction motor neuron counts tandem with altered (p<0.01). successfully displayed genetic markers post-CRISPR editing, indicating 95% editing efficiency. Furthermore, interactions between established neurodegenerative pathways identified. Conclusion: Mine findings highlight pivotal role targets offering potential avenues for early detection therapeutic interventions. intricate interplay these known disease underscores need integrated approach understand mechanisms holistically.

Language: Английский

Citations

0