Anti-fibrillization effects of sulfonamide derivatives on α-synuclein and hyperphosphorylated tau isoform 1N4R.

ABSTRACT: In contrast to Aβ plaques, the spatiotemporal distribution of neurofibrillary tangles of hyperphosphorylated tau (p-tau) predicts cognitive impairment in Alzheimer's disease (AD), underscoring the key pathological role of p-tau and the utmost need to develop AD therapeutics centering upon the control of p-tau aggregation and cytotoxicity. Our drug discovery program is focused on compounds that prevent the aggregation and cytotoxicity of p-tau moieties of the tau isoform 1N4R due to its prevalence (1 N) and long-distance trans-synaptic propagation (4R). We prepared and tested twenty-four newly synthesized small molecules representing the urea (1, 2, 3), sulfonylurea (4), and sulfonamide (5-24) series and evaluated their anti-aggregation effects with biophysical m

SUBMITTER: Fortin JS 

PROVIDER: S-EPMC9614895 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature