Summary Parkinson’s disease (PD), an adult neurodegenerative disorder, has been clinically linked to lysosomal storage disorder, Gaucher disease (GD), but the mechanistic connection has been unknown. Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes accumulation of a-synuclein (a-syn), and results in neurotoxicity through aggregation dependent mechanisms. GlcCer, the GCase substrate, directly influenced amyloid formation of purified a-syn by stabilizing soluble oligomeric intermediates. We further demonstrate that a-syn inhibits the lysosomal activity of normal GCase in neurons and idiopathic PD brain, suggesting that GCase depletion contributes to the pathogenesis of sporadic synucleinopathies. These findings suggest that the bidirectional effect of a-syn and GCase forms a positive feedback loop that may lead to a self-propagating disease. Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies.

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Two vanillin-based photocurable, thermally reprocessable, and chemically recyclable imine thermosets were successfully designed. The vanillin vitrimer resins were synthesized through a protocol with a two-step reaction: methacrylation and imination with diamine or triamine. The obtained vinyl ester resins with imine bonds and vinyl groups could be photocured into thermosets in 10 min at room temperature. The cured thermosets had good solvent resistance against common solvents, good thermal stability up to about 250 °C as measured by thermogravimetry, and high storage modulus (1.6−3.4 GPa as determined by dynamic mechanical analysis). Owing to the reversibility of the imine bond, both thermosets exhibited typical vitrimer behavior including stress relaxation and thermal reprocessability, while their activation energy for the imine exchange reaction and recovery ratio of tensile stress after reprocessing varied due to different cross-linking densities. Furthermore, both thermosets could be chemically recycled in hexylamine through an imine exchange reaction. The presented new strategy, thus, paves the way for production of fast-curing, chemically and thermally stable, but still thermally reprocessable and chemically recyclable imine vitrimers from abundant biobased building blocks.

A series of kraft lignin based thermosets were successfully synthesized by a one-pot heat curing method composed of lignin, PEG400, and citric acid through esterification reactions with water as the only produced byproduct. The polyester thermosets were prepared by varying the ratio of lignin and PEG400 in combination with citric acid as the cross-linker. Lignin and PEG400 were chosen as the rigid and soft segments, respectively, to tailor the thermal mechanical properties of the thermosets. An increase of lignin content from 20 to 40 wt % facilitated an increase in the cross-linking density and aromatic content. This was reflected in the storage modulus at 25 °C, which increased from 5.7 to 2000 MPa, and the glass transition temperature, which increased from −0.3 to 102 °C. At the same time, the tensile strength changed from 1.2 to 34.3 MPa. The mechanical properties were, thus, tunable from flexible to rigid, demonstrating a significantly high storage modulus and tensile strength for a biobased thermoset. Furthermore, a superb thermally stimulated shape memory property was illustrated. This is promising for the use of commercial kraft lignin as a building block for versatile applications.

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