Nanotechnology-mediated therapeutic strategies against synucleinopathies in neurodegenerative disease

Synucleinopathies are a subset of debilitating neurodegenerative disorders for which clinically approved therapeutic options to either halt or retard disease progression are currently unavailable. Multiple synergistic pathological mechanisms in combination with the characteristic misfolding of proteins are attributable to disease pathogenesis and progression. This complex interplay, as well as the difficult and multiscale nature of therapeutic delivery into the central nervous system, make finding effective treatments difficult. Nanocarriers (NCs) are a class of materials that can significantly improve therapeutic brain delivery and enable multifunctional therapies. In this review, an update on the known pathology of synucleinopathies is presented. Then, NC-enabled therapeutics designed to target the multiple mechanisms by combination therapies and multiscale targeting methods is reviewed. The implications of these strategies are synthesized and evaluated to suggest opportunities for the rational design of anti-neurodegenerative NC therapeutics.

Automated summary

Synucleinopathies are debilitating neurodegenerative disorders with no clinically approved therapeutic options. Multiple synergistic pathological mechanisms and misfolding of proteins contribute to disease progression, making treatment challenging. Nanocarriers can improve brain delivery of therapeutics and enable multifunctional therapies.