The aggregation of the amyloidogenic protein α-synuclein (α-Syn) into toxic oligomers and mature fibrils is the major pathological hallmark of Parkinson's disease (PD). Small molecules that inhibit α-Syn aggregation thus may be useful therapeutics for PD. Mannitol and naphthoquinone-tryptophan (NQTrp) have been shown in the past to inhibit α-Syn aggregation by different mechanisms. Herein, we tested whether the conjugation of Mannitol and NQTrp may result in enhance efficacy toward α-Syn. The molecules were conjugated either by a click linker or via a PEG linker. The effect of the conjugate molecules on α-Syn aggregation in vitro was monitored using Thioflavin T fluorescence assay, circular dichroism, transmission electron microscopy, and Congo red birefringence assay. One of the conjugate molecules was found to be more effective than the two parent molecules and as effective as a mixture of the two. The conjugate molecules attenuated the disruptive effect of α-Syn on artificial membrane of Large Unilamellar Vesicles as monitored by dye leakage assay. The conjugates were found to be have low cytotoxicity and reduced toxicity of α-Syn toward SH-SY5Y neuroblastoma cells. These novel designed entities can be attractive scaffold for the development of therapeutic agents for PD.

Tryptophan–glucosamine conjugates efficiently inhibit tau-derived PHF6-peptide fibrillization and disrupt its preformed fibrils at very low concentrations.

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Aggregation of amyloid‐β (Aβ) plays important roles in the progression of Alzheimer's disease (AD), and various carbon‐based nanomaterials have been shown to significantly inhibit aggregation of Aβ. A new member of the family of two‐dimensional (2D) nanomaterials, black phosphorus (BP), has been successfully prepared. Compared to other nanomaterials, BP has a higher surface‐to‐volume ratio, so it has strong adsorption ability for Aβ, and can thereby regulate the aggregation of Aβ. Herein, black phosphorus (BP) nanomaterials are proposed to regulate the aggregation of Aβ for the first time, and the corresponding mechanism is clarified. This work provides new insight into the development of BP‐based strategies to prevent amyloidosis.

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The aggregation of amyloid proteins has been suggested to be the main cause of multiple human disorders; for example, amyloid β aggregates in Alzheimer's disease and α-synuclein aggregates in Parkinson's disease. In the search for therapeutic medicines, many molecules have been discovered and developed to modulate the aggregation of amyloid proteins. This century has witnessed the flourishing growth of supramolecular chemistry, and some biocompatible macrocycles have been proven to inhibit the aggregation of some amyloid proteins via host-guest interactions and could thus be used for the prevention or treatment of related diseases. Here, we review the application of macrocycles in modulating the aggregation of amyloid proteins.

Clearance of amyloid β (Aβ) by immunotherapy is one of the fancy methods to treat Alzheimer's disease (AD). However, the failure of some clinical trials suggested that there may be something ignored in the past development of immunotherapy. Pyroglutamate-3 Aβ (Aβ), which was found to be abundant in the patients' brain, has attracted much attention after the report that Aβ could serve as a template to exacerbate the aggregation of Aβ. In addition, Aβ could not be recognized by the antibodies targeting the N-terminus of Aβ, suggesting that Aβ maybe the ignored one. Indeed, passive immunization targeting Aβ has shown some beneficial results, while active immunotherapy has not been extensively studied. In the present study, we designed and synthesized a novel peptide vaccine targeting Aβ, which contains Aβ as B cell epitope and P2 as T cell epitope. We showed that this vaccine could induce strong antibody response to Aβ. We also showed that prophylactic immunization of AD model mice with our vaccine could reduce Aβ plaques and rescue cognitive decline. This new kind of Aβ vaccine will open up new directions for AD immunotherapy.

Through the addition of nano-silicon dioxide in the pure polyphenylene sulfide, the masterbatches were obtained, then using melt spinning technology to prepare SiO2/PPS fiber. The structure and heat-resistant properties of samples were characterized by transmission election microscopy (TEM), infrared spectrum (IR), differential scanning calorimeter (DSC) and other measurements. The experiment results indicate that the mechanical and heat resistance properties of PPS fiber were improved after adding the content of 1%wt nano-silicon dioxide. When the fiber was heated at 230°C for 24 hours, the breaking strength and elongation increased by 2.412cN/dtex and 11.90% compared to the pure PPS fiber. Moreover, the working temperature raised by 50°C.