Evan T. Powers

TL;DR: It is proposed that small molecules can enhance proteostasis by binding to and stabilizing specific proteins (pharmacologic chaperones) or by increasing the protestasis network capacity (proteostasis regulators) and that such therapeutic strategies, including combination therapies, represent a new approach for treating a range of diverse human maladies.

TL;DR: The molecular and structural basis of TTR tetramer stabilization by tafamidis is described, suggesting that binding stabilizes the weaker dimer-dimer interface against dissociation, the rate-limiting step of amyloidogenesis.

TL;DR: A series of transthyretin amyloidosis inhibitors that functioned by increasing the kinetic barrier associated with misfolding, preventing amyloidsogenesis by stabilizing the native state.

TL;DR: The improved eNMDAR antagonist NitroMemantine, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from Aβ-induced damage both in vitro and in vivo.

TL;DR: FlAsH monitoring of Cys-Cys-Aβ 1-40 aggregation provides compelling evidence that Aβ1-40 very rapidly and efficiently forms spherical oligomers in vitro that are kinetically competent to slowly convert to amyloid fibrils by a nucleated conformational conversion mechanism (seedable).