Abnormal deposition and intercellular propagation of α-synuclein plays a central role in the pathogenesis of disorders such as Parkinson's Disease (PD) and dementia with Lewy bodies (DLB). Previous studies demonstrated that immunization against α-synuclein resulted in reduced α-synuclein accumulation and synaptic loss in a transgenic (tg) mouse model, highlighting the potential for immunotherapy. However, the mechanism by which immunization prevents synucleinopathy-associated deficits remains unknown. Here, we show that antibodies against α-synuclein specifically target and aid in clearance of extracellular α-synuclein proteins by microglia, thereby preventing their actions on neighboring cells. Antibody-assisted clearance occurs mainly in microglia through the Fcγ receptor, and not in neuronal cells or astrocytes. Stereotaxic administration of antibody into the brains of α-synuclein tg mice prevented neuron-to-astroglia transmission of α-synuclein and led to increased localization of α-synuclein and the antibody in microglia. Furthermore, passive immunization with α-synuclein antibody reduced neuronal and glial accumulation of α-synuclein and ameliorated neurodegeneration and behavioral deficits associated with α-synuclein overexpression. These findings provide an underlying mechanistic basis for immunotherapy for PD/DLB and suggest extracellular forms of α-synuclein as potential therapeutic targets.

Deposition of α-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson’s disease (PD). Although recent evidence has suggested that cell-to-cell transmission of α-synuclein aggregates drives the progression of PD, the mechanism by which α-synuclein aggregates spread remains undefined. Here, we show that α-synuclein aggregates are perpetually transmitted through a continuous cycle involving uptake of external aggregates, co-aggregation with endogenous α-synuclein, and exocytosis of the co-aggregates. Moreover, we found that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promoted propagation of α-synuclein aggregates. These studies define how α-synuclein aggregates spread among neuronal cells and explain how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies.

Heterostructures composed of two-dimensional black phosphorus (2D BP) with unique physical/chemical properties are of great interest. Herein, we report a simple solvothermal method to synthesize in-plane BP/Co P heterostructures for electrocatalysis. By using the reactive edge defects of the BP nanosheets as the initial sites, Co P nanocrystals are selectively grown on the BP edges to form the in-plane BP/Co P heterostructures. Owing to disposition on the original defects of BP, Co P improves the conductivity and offers more active electrocatalytic sites, so that the BP/Co P nanosheets exhibit better and more stable electrocatalytic activities in the hydrogen evolution and oxygen evolution reactions. Our work not only extends the application of BP to electrochemistry, but also provides a new idea to improve the performance of BP by utilization of defects. Furthermore, this strategy can be extended to produce other BP heterostructures to expand the corresponding applications.

Nanomedicines intergrating both therapy and diagnosis functions provide a promising strategy for anticancer treatment. As novel two-dimensional materials, black phosphorus nanosheets (BPs) possess unique properties for biomedical applications, pratically for photothermal therapy (PTT) of cancer, but their lack of air and water stability may hinder their application. Herein, a covalent functionalization strategy based on Nile Blue (NB) dye via diazonium chemistry is established to modify BPs, not only enhancing the stability of BPs but also rendering BPs via nearinfrared (NIR) fluorescence, forming a novel multifunctional nanomedicine with both PTT and NIR imaging capabilities. In vitro tests demonstrate that the dye-modified BPs (named NB@BPs) have good biocompatibility and exhibit strong PTT and NIR imaging efficiency. In vivo experiments show that the NB@BPs can mark the tumor site with red fluorescence and lead to efficient tumor ablation under NIR irradiation. These results reveal a potential BP-based nanomedicine with multiple functionalities that bode well for anticancer applications.