Physicochemically Defined Nanoscale Graphene Oxide Modulates Fibril-Related α-Synuclein and Attenuates Parkinsonian Pathology In Vivo.

Nanoscale graphene oxide (nGO) has emerged as a promising biomaterial for neurological applications because its ultrasmall dimensions, oxygen-containing surface chemistry, and colloidal behavior may support biologically relevant interfacial interactions. Here, we physicochemically defined nGO synthesized by a modified Taylor-Couette method using transmission electron microscopy, atomic force microscopy, particle size analysis, zeta potential measurement, X-ray diffraction, and Fourier-transform infrared spectroscopy. The resulting nGO exhibited ultrasmall lateral dimensions together with characteristic oxygen-containing functional groups and a negative zeta potential in distilled water. In a time-course dot blot assay using α-synuclein (α-syn) preformed fibrils, incubation with nGO was associated with reduced fibril-related α-syn immunoreactivity without a statistically significant change in total α-syn signal; a fractionation assay further revealed fraction-dependent differences in antibody-detectable α-syn signals. We then evaluated behavioral and nigral histological outcomes following intraperitoneal nGO administration in a rat model of Parkinson's disease induced by unilateral adeno-associated virus-mediated overexpression of A53T α-syn in the substantia nigra. nGO administration was associated with improved stepping performance, greater preservation of nigral tyrosine hydroxylase-positive cells, reduced nigral α-syn immunoreactivity, and decreased Iba-1-positive area. Collectively, these findings support further consideration of physicochemically defined, unmodified nGO as an active biomaterial associated with fibril-related α-syn readouts in vitro and functional and histological outcomes consistent with neuroprotection in vivo.