Alzheimer's disease (AD) is currently one of the most difficult and challenging diseases to treat. Based on the ‘multi-target-directed ligands’ (MTDLs) strategy, we designed and synthesised a series of new compounds against AD by combining the pharmacophores of resveratrol and clioquinol. The results of biological activity tests showed that the hybrids exhibited excellent MTDL properties: a significant ability to inhibit self-induced β-amyloid (Aβ) aggregation and copper(II)-induced Aβ aggregation, potential antioxidant behaviour (ORAC-FL value of 0.9–3.2 Trolox equivalents) and biometal chelation. Among these compounds, (E)-5-(4-hydroxystyryl)quinoline-8-ol (10c) showed the most potent ability to inhibit self-induced Aβ aggregation (IC50 = 8.50 μM) and copper(II)-induced Aβ aggregation and to disassemble the well-structured Aβ fibrils generated by self- and copper(II)-induced Aβ aggregation. Note that 10c could also control Cu(I/II)-triggered hydroxyl radical (OH˙) production by halting copper redox cycling via metal complexation, as confirmed by a Cu–ascorbate redox system assay. Importantly, 10c did not show acute toxicity in mice at doses of up to 2000 mg kg−1 and was able to cross the blood–brain barrier (BBB), according to a parallel artificial membrane permeation assay. These results indicate that compound 10c is a promising multifunctional compound for the development of novel drugs for AD.

Lattices of controlled thermal expansion are presented based on planar chiral lattice structure with Poisson's ratio approaching −1. Thermal expansion values can be arbitrarily large positive or negative. A lattice was fabricated from bimetallic strips and the properties analyzed and studied experimentally. The effective thermal expansion coefficient of the lattice is about α=−3.5×10−4K−1. This is much larger in magnitude than that of constituent metals. Nodes were observed to rotate as temperature was changed corresponding to a Cosserat thermoelastic solid.

A series of tacrine-propargylamine derivatives were synthesised and evaluated as possible anti-Alzheimer's disease (AD) agents. Among these derivatives, compounds 3a and 3b exhibited superior activities and a favourable balance of AChE and BuChE activities (3a: IC50 values of 51.3 and 77.6 nM; 3b: IC50 values of 11.2 and 83.5 nM). Compounds 3a and 3b also exhibited increased hAChE inhibitory activity compared with tacrine by approximately 5- and 28-fold, respectively, and low neurotoxicity. Importantly, these compounds also had lower hepatotoxicity than tacrine. Based on these results, compounds 3a and 3b could be considered as potential lead compounds for the treatment of AD and other AChE related diseases, such as schizophrenia, glaucoma and myasthenia gravis.

Tripterygium wilfordii Hook F. (TWHF), a traditional Chinese medicine, has been widely used to treat autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis in China. Recently, studies have demonstrated that the bioactive components of TWHF have effective therapeutic potential for neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis. In this paper, we summarize the research progress of triptolide and celastrol (the two major TWHF components) as well as their analogues in the treatment of neurodegenerative diseases. In addition, we review and discuss the molecular mechanisms and structure features of those two bioactive TWHF components, highlighting their therapeutic promise in neurodegenerative diseases.

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