Many neurodegenerative diseases, referred to as misfolding diseases, are characterized by the formation and accumulation of
pathological extracellular and intracellular misfolded aggregates. Ageing is considered the major risk factor for neurodegenerative disorders
and, due to increase of mean lifespan, the clinical relevance is growing dramatically with a urgent need to find new effective therapeutic
approaches. The intracellular antibody technology is a gene-based strategy which exploits the specificity of recombinant antibodies
to neutralize or modify the function of intracellular and extracellular target antigens. Intrabodies can potentially recognize all the
pathological conformers of a misfolding-prone protein, and therefore they are emerging as therapeutic agents for the treatment of misfolding
diseases as well as molecular tools for the understanding of their pathogenesis.
Here we focus on the application of intrabodies against two major age-related neurodegenerative disorders, Alzheimer’s disease (AD)
and Parkinson’s disease (PD) and the description of in vivo gene delivery systems available for their potential entering in the clinical setting.