Epitope-specific antibody fragments block aggregation of AGelD187N, an aberrant peptide in gelsolin amyloidosis.

Aggregation of aberrant fragment of plasma gelsolin, AGelD187N, is a crucial event underlying the pathophysiology of Finnish gelsolin amyloidosis, an inherited form of systemic amyloidosis. The amyloidogenic gelsolin fragment AGelD187N does not play any physiological role in the body, unlike most aggregating proteins related to other protein misfolding diseases. However, no therapeutic agents that specifically and effectively target and neutralize AGelD187N exist.

5-HT receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines.

In this study, we present the discovery and pharmacological characterization of a new series of 6-piperazinyl-7-azaindoles. These compounds demonstrate potent antagonism and selectivity against the 5-HT receptor. Our research primarily focuses on optimizing the lead structure and investigating the structure-activity relationship (SAR) of these compounds.

Development of an in vitro aggregation assay for long synthetic polypeptide, amyloidogenic gelsolin fragment AGelD187N 173-242.

Aggregation of the gelsolin protein fragment is the hallmark of the hereditary systemic disease gelsolin amyloidosis. As with other protein misfolding diseases, there is an urgent need for efficient disease-modifying treatment for gelsolin amyloidosis. The formation of amyloids can be reproduced by incubating the disease-causing amyloidogenic 8 kDa polypeptide, 70-residue gelsolin protein fragment, AGelD187N 173-242, in vitro and monitoring the process by thioflavin T dye.

Feasibility and patient acceptability of a commercially available wearable and a smart phone application in identification of motor states in parkinson's disease.

In the quantification of symptoms of Parkinson's disease (PD), healthcare professional assessments, patient reported outcomes (PRO), and medical device grade wearables are currently used. Recently, also commercially available smartphones and wearable devices have been actively researched in the detection of PD symptoms. The continuous, longitudinal, and automated detection of motor and especially non-motor symptoms with these devices is still a challenge that requires more research.

Tasipimidine-the pharmacological profile of a novel orally active selective α-adrenoceptor agonist.

The pharmacological profile of tasipimidine, a novel orally active α-adrenoceptor agonist developed for situational anxiety and fear in dogs, was studied in various in vitro and in vivo models. In the cell assays, tasipimidine demonstrated binding affinity and full agonism on the human α-adrenoceptors with a pEC50 of 7.57, while agonism on the α-and α-adrenoceptors and the rodent α-adrenoceptor was weaker, resulting in pEC50 values of 6.