RESUMO
AIM: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized muscle atrophy, paralysis, and even death. Mitochondrial damage and neuroinflammation play key roles in the pathogenesis of ALS. In the present study, the efficacy of A-1, a derivative of arctigenin with AMP-activated protein kinase (AMPK) and silent information regulator 1 (SIRT1) activation for ALS, was investigated. METHODS: A-1 at 33.3 mg/kg was administrated in SOD1G93A transgenic mice orally from the 13th week for a 6-week treatment period. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes, and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl, and immunohistochemistry staining. Protein expression was detected with proteomics analysis, Western blotting, and ELISA. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. RESULTS: A-1 administration in SOD1G93A mice enhanced mobility, decreased skeletal muscle atrophy and fibrosis, mitigated loss of spinal motor neurons, and reduced glial activation. Additionally, A-1 treatment improved mitochondrial function, evidenced by elevated ATP levels and increased expression of key mitochondrial-related proteins. The A-1 treatment group showed decreased levels of IL-1ß, pIκBα/IκBα, and pNF-κB/NF-κB. CONCLUSIONS: A-1 treatment reduced motor neuron loss, improved gastrocnemius atrophy, and delayed ALS progression through the AMPK/SIRT1/PGC-1α pathway, which promotes mitochondrial biogenesis. Furthermore, the AMPK/SIRT1/IL-1ß/NF-κB pathway exerted neuroprotective effects by reducing neuroinflammation. These findings suggest A-1 as a promising therapeutic approach for ALS.
Assuntos
Proteínas Quinases Ativadas por AMP , Esclerose Lateral Amiotrófica , Furanos , Interleucina-1beta , Camundongos Transgênicos , NF-kappa B , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Sirtuína 1 , Animais , Sirtuína 1/metabolismo , Camundongos , NF-kappa B/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Furanos/farmacologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/metabolismo , Interleucina-1beta/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Lignanas/farmacologia , Lignanas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Masculino , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Neurônios Motores/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Medula Espinal/metabolismoRESUMO
A 7-year-old boy was misdiagnosed as having contact dermatitis due to itching and redness of the eyelids. Later, with the assistance of a slit lamp, active pubic lice on the eyelid margin were discovered. Microorganisms and insect eggs were mechanically removed, and itching and redness symptoms complete disappeared after 1 week. [J Pediatr Ophthalmol Strabismus. 2024;61(2)e13-e15.].
Assuntos
Pestanas , Infestações por Piolhos , Phthirus , Animais , Masculino , Humanos , Criança , Infestações por Piolhos/diagnóstico , PruridoRESUMO
OBJECTIVES: Arctigenin (ATG) is a natural product with a variety of biological activity, which can improve the pathological changes of Alzheimer's disease (AD) model mice through multiple mechanisms. This study aims to further elucidate the potential mechanism by which ATG improves memory impairment in AD mice. METHODS: Here, we used pR5 mice as an experimental model, and ATG was administered continuously for 90 days. Novel object recognition, Y-maze, and Morris water maze were used to evaluate the therapeutic effect of ATG on memory impairment in AD mice. Immunohistochemical and immunofluorescence analyses were used to evaluate the effects of ATG on tau hyperphosphorylation and neuroinflammation, respectively. Finally, proteomics techniques were used to explore the possible mechanism of ATG. KEY FINDINGS: ATG significantly improved memory impairment in pR5 mice and inhibited tau phosphorylation in the hippocampus and neuroinflammation in the cortex. According to the proteomic analysis, the altered cognitive function of ATG was associated with the proteins of the tricarboxylic acid cycle and the electron transport chain. CONCLUSION: These results suggest that ATG is a potential therapeutic agent for diseases related to aberrant energy metabolism that can treat AD by improving mitochondrial function.