Nanoparticle assisted remodeling of proteotoxic SOD1 mutants alters the bio-interface of the functional interaction of microtubules and kinesin motors

Transport deficits with motor neuron degeneration have been implicated in amyotrophic lateral sclerosis (ALS). We report a bio-mimetic system comprise 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 recover the impaired motor stepping by remodeling the A4V SOD1 rather than stabilizing microtubule 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.