RESUMO
Alzheimer's disease (AD) is the most prevalent but still incurable neurodegenerative form of dementia. Early diagnosis and intervention are crucial for delaying the onset and progression of the disease. We herein report a novel fluoro-substituted cyanine, F-SLOH, which exhibits good Aß oligomer selectivity with a high binding affinity, attributed to the synergistic effect of strong π-π stacking and intermolecular CH···O and CH···F interactions. The selectivity towards the Aß oligomers in the brain was ascertained by in vitro labelling on tissue sections and in vivo labelling through the systemic administration of F-SLOH in 7 month APP/PS1 double transgenic (Tg) and APP/PS1/Tau triple Tg mouse models. F-SLOH also shows remarkably effective inhibition on Aß aggregation and highly desirable neuroprotective effects against Aß-induced toxicities, including the inhibition of ROS production and Ca2+ influx. Its excellent blood-brain barrier (BBB) penetrability and low bio-toxicity further support its tremendous potential as a novel theranostic agent for both early diagnosis and therapy of AD.
RESUMO
In the present study, N-methyl-D-aspartate receptor 2B (NR2B)-specific siRNA was applied in parkinsonian models. Our previous results showed that reduction in expression of N-methyl-D-aspartate receptor 1 (NR1), the key subunit of N-methyl-D-aspartate receptors, by antisense oligos ameliorated the motor symptoms in the 6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease (PD).
Assuntos
Neurônios Dopaminérgicos/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Fármacos Neuroprotetores/metabolismo , RNA Interferente Pequeno/biossíntese , Receptores de N-Metil-D-Aspartato/biossíntese , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Ativação Enzimática/fisiologia , Masculino , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/prevenção & controle , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genéticaRESUMO
This is the first work that revealed the neuro-protective effect of functionalized quantum dots against the cytotoxicity induced by beta-amyloid peptides. This study gives insight into the future treatment of Alzheimer's disease. It opens many avenues for the development of the next generation nanotechnology for biomedical and therapeutic applications.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/química , Carbazóis/química , Corantes Fluorescentes/química , Doença de Alzheimer/tratamento farmacológico , Animais , Carbazóis/farmacologia , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos , Estrutura MolecularRESUMO
Confocal fluorescence demonstrates that single molecules of dye-labelled Cytochrome C or B5 containing paramagnetic Fe(III) can be magnetically placed into the interstices of super-crystal which is composed of three dimensional regular arrays of Fe(3)O(4) nanoparticles.