Nanopolyphenol rejuvenates microglial surveillance of multiple misfolded proteins through metabolic reprogramming

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Research progress in immunotherapy for glioblastoma / 药学学报

Glioma is the most common primary intracranial tumor, among which glioblastoma (GBM) is the most malignant subtype. Because of its high heterogeneity and invasiveness, GBM can't be completely removed by surgical resection and is also resistance to chemotherapy and radiotherapy. Even after a standard therapy, the median survival time is only 14.6 months, the five-year survival rate is less than 10%, and the relapse of GBM is common. Immunotherapy, a new treatment paradigm, treats cancer through regulating the autologous immune system and the tumor microenvironment. As a promising method to improve the prognosis of GBM, immunotherapy has attracted more and more attention. This paper gives a review to the difficulty, the mainly existing strategies and the bottlenecks in GBM immunotherapy, aiming at providing new direction to improve the prognosis of GBM patients.