Abnormal cytoplasmic localization and accumulation of pathological transactive response DNA binding protein of 43 kDa (TDP-43) underlies several devastating diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP ...
Optimal pharmacokinetic (PK) properties of therapeutic monoclonal antibodies (mAbs) are essential to achieve the desired pharmacological benefits in patients. To accomplish this, we followed an approach comprising structure-based mAb charge engineering in ...
Tau aggregates represent a critical pathology in Alzheimer's disease (AD) and other forms of dementia. The extent of Tau neurofibrillary tangles across defined brain regions corresponds well to the observed level of cognitive decline in AD. Compound 1 (PI- ...
Tau has become an attractive alternative target for passive immunotherapy efforts for Alzheimer's disease (AD). The anatomical distribution and extent of tau pathology correlate with disease course and severity better than other disease markers to date. We ...
The compound screening was initiated with a direct staining assay to identify compounds binding to Tau aggregates and not Abeta plaques using human brain sections derived from late stage Alzheimer's disease donors. The binding of Tau aggregate selective co ...
A concise synthesis of pharmaceutically useful (R)-tert-butyl N-(2-bromo-9-methyl-6,7,8,9-tetrahydro-5H-pyrido [2,3-b ] indol-6-yl) -N-methylcarbamate building block 11 is described. The racemic intermediate 17 was prepared in a single step from 2-bromo-6- ...
The aggregation of intracellular tau protein is a major hallmark of Alzheimer's disease (AD). The extent and the stereotypical spread of tau pathology in the AD brain are correlated with cognitive decline during disease progression. Here we present an in-d ...
It is assumed that amyloid-beta aggregation is a crucial event in the pathogenesis of Alzheimer's disease. Novel 2,6-disubstituted pyridine derivatives were designed to interact with the beta-sheet conformation of A beta via donor-acceptor-donor hydrogen b ...
Accumulation of amyloid-beta (A beta) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer's disease (AD). The precise pathological species of A beta remains elusive although evidence suggests soluble oligomers may be prima ...
Scientists working in the fields of Alzheimer's disease and, in particular, cognitive enhancers are very productive. The review "Cognitive enhancers (nootropics): drugs interacting with receptors" was accepted for publication in July 2012. Since then, new ...
