A fluoro-substituted cyanine showing reliable in vivo labelling of Aβ oligomers and potent neuroprotective effect against Aβ-induced toxicities is reported as a novel theranostic agent for the early diagnosis and therapy of Alzheimer's disease.

No abstract

Aggregation ausgeschlossen: Carbazol‐basierte Cyaninfluorophore binden selektiv an das Aβ(1–40)‐Peptid und dessen Aggregate, die zur Entstehung der Alzheimer‐Krankheit führen. Ein solcher Fluorophor, SLOH, hemmt wirksam die Bildung von Aβ(1–40)‐Fibrillen (siehe Schema); da er die Blut‐Hirn‐Schranke passieren kann, ist er ein potenzielles Alzheimer‐Therapeutikum.

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 amelio-rated the motor symptoms in the 6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease (PD) [Lai et al.: Neurochem Int 2004;45:11-22]. To further the investigation on the efficacy of gene silencing, small interference RNA (siRNA) specific for the NR2B subunit was designed and administered in the striatum of 6-OHDA-lesioned rats. The present results show that administration of NR2B-specific siRNA decreased the number of apomorphine-induced rotations in the lesioned rats and that there was a significant reduction in NR2B proteins levels after NR2B-specific siRNA administration. Furthermore, attenuation of the loss of dopaminergic neurons was found in both the striatal and substantia nigra regions of the 6-OHDA-lesioned rats that had been continuously infused with siRNA for 7 days. In addition, a significant upregulation of p-p44/42 MAPK (ERK1/2; Thr202/Tyr204) and p-CREB (Ser133) in striatal neurons was found. These results suggest that application of the gene silencing targeting NR2B could be a potential treatment of PD, and they also revealed the possibility of NR2B-specific siRNA being involved in the prosurvival pathway.