Discovery of small molecule benzothiazole and indole derivatives tackling tau 2N4R and α-synuclein fibrils.

Tau and α-synuclein aggregates are the main histopathological hallmarks present in Alzheimer's disease (AD), Parkinson's disease (PD), and other neurodegenerative disorders. Intraneuronal hyperphosphorylated tau accumulation is significantly connected to the degree of cognitive impairment in AD patients. In particular, the longest 2N4R tau isoform has a propensity to rapidly form oligomers and mature fibrils.

1,4-Diurea- and 1,4-Dithiourea-Substituted Aromatic Derivatives Selectively Inhibit α-Synuclein Oligomer Formation .

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting the elderly population worldwide. In PD, the misfolding of α-synuclein (α-syn) results in the formation of inclusions referred to as Lewy bodies (LB) in midbrain neurons of the substantia nigra and other specific brain localizations, which is associated with neurodegeneration. There are no approved strategies to reduce the formation of LB in the neurons of patients with PD.