NQTrp

NQTrp, also known as 1,4-naphthoquinon-2-yl-L-tryptophan, is an inhibitor of the Alzheimer’s disease-associated β-amyloid [1].

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the early soluble oligomeric species of Aβ plays a fundamental role in the pathogenesis of AD [1]. The Aβ peptide results from the cleavage of the amyloid precursor protein (APP) by the β- and γ-secretases and the predominant Aβ peptides found in the brain are 40 (Aβ1-40) and 42 (Aβ1-42) residues [2].

In the oligomer inhibition assay and ThT fibril inhibition assay, NQTrp completely inhibited Aβ oligomerization and fibrillization. In cultured neural cells, NQTrp dose-dependently inhibited Aβ to assemble into toxic oligomers. In rat PC12 neuronal cell line, NQTrp significantly inhibited the cytotoxic effect of the Aβ oligomers and increased the viability of the cells [1].

In a Drosophila model of AD, NQTrp prolonged the life span of Aβ1–42-expressing flies. Aβ1–42-expressing flies with NQTrp displayed dramatic improvement, behaving almost identical to the control classes. The brains of these flies showed a significant reduction in oligomeric species of Aβ [1].

References:
[1].  Scherzer-Attali R, Pellarin R, Convertino M, et al. Complete phenotypic recovery of an Alzheimer's disease model by a quinone-tryptophan hybrid aggregation inhibitor. PLoS One. 2010 Jun 14;5(6):e11101.
[2].  Zhang T, Xu W, Mu Y, et al. Atomic and dynamic insights into the beneficial effect of the 1,4-naphthoquinon-2-yl-L-tryptophan inhibitor on Alzheimer's Aβ1-42 dimer in terms of aggregation and toxicity. ACS Chem Neurosci. 2014 Feb 19;5(2):148-59.