Nanoparticle Assisted Remodeling of Proteotoxic SOD1 Mutants Alters the Biointerface of the Functional Interaction of Microtubules and Kinesin Motors.

Abstract

Transport deficits with motor neuron degeneration have been implicated in amyotrophic lateral sclerosis (ALS). We report a biomimetic system composed of microtubules/kinesin motor that mimics the dysregulated motor dynamics of ALS. Pathogenic ALS mutants A4V SOD1 completely shut off motility. Treatment with 5 nm citrate coated gold nanoparticles recovers the impaired motor stepping by remodeling the A4V SOD1 rather than stabilizing microtubules or protein folding. Instead, gold nanoparticles alter the protein by a mechanism that reforms protein elements of A4V SOD1, in turn fixing the aberrant interaction of kinesin with microtubules. Reinstating kinesin motility holds potential for managing debilitating ALS.