Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder DOI Creative Commons

Kang-Ni Chen,

Qilin Peng,

Danfeng Cao

et al.

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 210, P. 110928 - 110928

Published: March 15, 2024

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as novel contributor of ferroptosis, recently discovered cell death mode the regulation brain function. However, role Lox-mediated ferroptosis ECD remains unknown. mouse model was established 2 months later following single injection kainic acid (KA) for. After chronic treatment with KA, mice were treated different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) Lox inhibitor BAPN. Additionally, hippocampal-specific knockout also constructed employed to validate ECD. Cognitive functions assessed using object recognition test (NOR) Morris water maze (MWM). Protein expression phosphorylated cAMP-response element binding (CREB), well-known molecular marker for evaluation performance, detected by Western blot. The protein distribution analyzed immunofluorescence. In KA-induced model, process activated according upregulation 4-HNE previously our group, namely, remarkably increased. Pharmacological inhibition BAPN at dose significantly increased discrimination index NOR decreased escape latency well augmented passing times within 60 s MWM model. deficiency hippocampus led pronounced improvement deficits These findings indicate regulatory factor, Lox, is Ablation either pharmacological intervention or genetic manipulation ameliorates impairment which suggest serves promising therapeutic target treating clinic.

Language: Английский

Synthesis, antioxidant and neuroprotective analysis of diversely functionalized α-aryl-N-alkyl nitrones as potential agents for ischemic stroke therapy DOI
Alejandro Escobar-Peso, Emma Martínez‐Alonso, Dimitra Hadjipavlou–Litina

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 266, P. 116133 - 116133

Published: Jan. 9, 2024

Language: Английский

Citations

3
Zhongfeng Decoction attenuates cerebral ischemia-reperfusion injury by inhibiting autophagy via regulating the AGE-RAGE signaling pathway DOI
Weitao Wang,

Wanshen Zhao,

Xiaoxiao Song

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 336, P. 118718 - 118718

Published: Aug. 23, 2024

Language: Английский

Citations

3
Development of Pharmacological Strategies with Therapeutic Potential in Ischemic Stroke DOI Creative Commons
Alejandro Escobar-Peso, Emma Martínez‐Alonso, Jaime Masjuán

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(12), P. 2102 - 2102

Published: Dec. 12, 2023

Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, the dependency that it generates being an important source of inequality. The lack treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is presented need. With this goal in mind, our research group's collaborative studies into cerebral ischemia subsequent reperfusion concluded there need develop compounds antioxidant radical scavenger features. In review, we summarize path taken toward identification lead potential candidates for treatment acute stroke. Evaluations capacity, neuroprotection primary neuronal cultures vivo experimental models ischemia, including neurological deficit score assessments, are conducted characterize biological efficacy various developed. Moreover, initial results preclinical development, dose-response studies, therapeutic window, long-term effect evaluation, reported. prompt these clinical trials encouraging regarding new drug developments aimed at successful therapy

Language: Английский

Citations

6
Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder DOI Creative Commons

Kang-Ni Chen,

Qilin Peng,

Danfeng Cao

et al.

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 210, P. 110928 - 110928

Published: March 15, 2024

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as novel contributor of ferroptosis, recently discovered cell death mode the regulation brain function. However, role Lox-mediated ferroptosis ECD remains unknown. mouse model was established 2 months later following single injection kainic acid (KA) for. After chronic treatment with KA, mice were treated different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) Lox inhibitor BAPN. Additionally, hippocampal-specific knockout also constructed employed to validate ECD. Cognitive functions assessed using object recognition test (NOR) Morris water maze (MWM). Protein expression phosphorylated cAMP-response element binding (CREB), well-known molecular marker for evaluation performance, detected by Western blot. The protein distribution analyzed immunofluorescence. In KA-induced model, process activated according upregulation 4-HNE previously our group, namely, remarkably increased. Pharmacological inhibition BAPN at dose significantly increased discrimination index NOR decreased escape latency well augmented passing times within 60 s MWM model. deficiency hippocampus led pronounced improvement deficits These findings indicate regulatory factor, Lox, is Ablation either pharmacological intervention or genetic manipulation ameliorates impairment which suggest serves promising therapeutic target treating clinic.

Language: Английский

Citations

1