Although emerging evidence suggests that the pathogenesis of Parkinson’s disease (PD) is closely related to the aggregation of alpha-synuclein (α-syn) in the midbrain, the clearance of α-syn remains an unmet clinical need. Here, we develop a simple and efficient strategy for fabricating the α-syn nanoscavenger for PD via a reprecipitation self-assembly procedure. The curcumin analogue-based nanoscavenger (NanoCA) is engineered to be capable of a controlled-release property to stimulate nuclear translocation of the major autophagy regulator, transcription factor EB (TFEB), triggering both autophagy and calcium-dependent exosome secretion for the clearance of α-syn. Pretreatment of NanoCA protects cell lines and primary neurons from MPP+-induced neurotoxicity. More importantly, a rapid arousal intranasal delivery system (RA-IDDS) was designed and applied for the brain-targeted delivery of NanoCA, which affords robust neuroprotection against behavioral deficits and promotes clearance of monomer, oligomer, and aggregates of α-syn in the midbrain of an MPTP mouse model of PD. Our findings provide a clinically translatable therapeutic strategy aimed at neuroprotection and disease modification in PD.

The root is the main organ of a plant for absorbing resources and whose spatial distribution characteristics play an important role in the survival of seedlings after afforestation. Chinese fir (Cunninghamia lanceolata) is one of China’s most important plantation species. To clarify the effects of propagation methods on root growth and spatial distribution characteristics of Chinese fir trees, sampled trees cultivated by seed germination, tissue culture, and asexual cutting of Chinese fir were taken as the research objects. The root morphology, geometric configuration, and spatial distribution characteristics of different trees were analyzed. The influence of geometric root morphology on its spatial distribution pattern was explored by correlation analysis, and the resource acquisition characteristics reflected by the roots of Chinese fir trees with different propagation methods are discussed. The main results showed that the root mean diameter (1.56 mm, 0.95 mm, and 0.97 mm), root volume (2.98 m3, 10.25 m3, and 4.07 m3), root tip count (397, 522, and 440), main root branch angle (61°, 50° and 32°) and other geometric configurations of Chinese fir under seed germination, tissue culture and rooted cutting respectively, were significantly different, which resulted in different distribution characteristics of roots in space. Chinese fir seed germination had noticeable axial roots, and the growth advantage was obvious in the vertical direction. A fishtail branch structure (TI = 0.87) was constructed. The shallow root distribution of tissue culture and rooted cutting was obvious, and belonged to the fork branch structure (TI = 0.71 and 0.74, respectively). There was a tradeoff in the spatial growth of the root system of Chinese fir trees with different propagation methods to absorb nutrients from heterogeneous soil patches. A negative correlation was present between the root system and root amplitude. There was an opposite spatial growth trend of Chinese fir trees with different propagation methods in the vertical or horizontal direction. In conclusion, selecting suitable propagation methods to cultivate Chinese fir trees is beneficial to root development and the “ideal” configuration formation of resource acquisition to improve the survival rate of Chinese fir afforestation.

Background Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. Results We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. Conclusions Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.