Nanowired delivery of antibodies to tau and neuronal nitric oxide synthase together with cerebrolysin attenuates traumatic brain injury induced exacerbation of brain pathology in Parkinson's disease.

Abstract

Concussive head injury (CHI) is one of the major risk factors for developing Parkinson's disease in later life of military personnel affecting lifetime functional and cognitive disturbances. Till date no suitable therapies are available to attenuate CHI or PD induced brain pathology. Thus, further exploration of novel therapeutic agents are highly warranted using nanomedicine in enhancing the quality of life of veterans or service members of US military. Since PD or CHI induces oxidative stress and perturbs neurotrophic factors regulation associated with phosphorylated tau (p-tau) deposition, a possibility exists that nanodelivery of agents that could enhance neurotrophic factors balance and attenuate oxidative stress could be neuroprotective in nature. In this review, nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies to neuronal nitric oxide synthase (nNOS) with p-tau antibodies was examined in PD following CHI in model experiments. Our results suggest that combined administration of nanowired antibodies to nNOS and p-tau together with cerebrolysin significantly attenuated CHI induced exacerbation of PD brain pathology. This combined treatment also has beneficial effects in CHI or PD alone, not reported earlier.