Accumulating evidence shows that Sirt1 regulates a variety of neurological functions through the deacetylation of many proteins besides histone; however, the literature on the relationship between Sirt1 and axonal outgrowth is limited. Here, we first demonstrated that Sirt1 was located in the axon, especially in the growth cone. Then, we found that genetic inhibition of Sirt1 retarded axonal development in embryonic hippocampal neurons, whereas genetic and pharmacologic upregulation of Sirt1 promoted not only the formation but also the elongation of axons. Sirt1 can deacetylate and thus activate Akt, and inhibition of Akt significantly reversed the axonogenesis induced by Sirt1 overexpression. We also found that Sirt1 inhibited the activity of glycogen synthase kinase 3 (GSK3), whereas activation of GSK3 could abolish the effect of Sirt1. These results suggest that Sirt1 promotes axonogenesis by deacetylating Akt and thereby activates the Akt/GSK3 pathway, which could be a promising therapeutic target for axonopathy.

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Evidence suggests that curcumin, the phytochemical agent in the spice turmeric, might be a potential therapy for Alzheimer's disease (AD). Its antioxidant, anti-inflammatory properties have been investigated extensively. Studies have also shown that curcumin can reduce amyloid pathology in AD. The underlying mechanism, however, is complex and is still being explored. In this study, we used the APPswe/PS1dE9 double transgenic mice, an AD model, to investigate the effects and mechanisms of curcumin in the prevention and treatment of AD. The water maze test indicated that curcumin can improve spatial learning and memory ability in mice. Immunohistochemical staining and Western blot analysis were used to test major proteins in β-amyloid aggregation, β-amyloid production, and β-amyloid clearance. Data showed that, 3 months after administration, curcumin treatment reduced Aβ40 , Aβ42 , and aggregation of Aβ-derived diffusible ligands in the mouse hippocampal CA1 area; reduced the expression of the γ-secretase component presenilin-2; and increased the expression of β-amyloid-degrading enzymes, including insulin-degrading enzymes and neprilysin. This evidence suggests that curcumin, as a potential AD therapeutic method, can reduce β-amyloid pathological aggregation, possibly through mechanisms that prevent its production by inhibiting presenilin-2 and/or by accelerating its clearance by increasing degrading enzymes such as insulin-degrading enzyme and neprilysin.

Effective treatments promoting axonal regeneration and functional recovery for spinal cord injury (SCI) are still in the early stages of development. Most approaches have been focused on providing supportive substrates for guiding neurons and overcoming the physical and chemical barriers to healing that arise after SCI. Although collagen has become a promising natural substrate with good compatibility, its low mechanical properties restrict its potential applications. The mechanical properties mainly rely on the composition and pore structure of scaffolds. For the composition of a scaffold, we used heparin sulfate to react with collagen by crosslinking. For the structure, we adopted a three-dimensional (3D) printing technology to fabricate a scaffold with a uniform pore distributions. We observed that the internal structure of the scaffold printed with a 3D bioprinter was regular and porous. We also found that both the compression modulus and strengths of the scaffold were significantly enhanced by the collagen/heparin sulfate composition compared to a collagen scaffold. Meanwhile, the collagen/heparin sulfate scaffold presented good biocompatibility when it was co-cultured with neural stem cells in vitro. We also demonstrated that heparin sulfate modification significantly improved bFGF immobilization and absorption to the collagen by examining the release kinetics of bFGF from scaffolds. Two months after implantating the scaffold into transection lesions in T10 of the spinal cord in rats, the collagen/heparin sulfate group demonstrated significant recovery of locomotor function and according to electrophysiological examinations. Parallel to functional recovery, collagen/heparin sulfate treatment further ameliorated the pathological process and markedly increased the number of neurofilament (NF) positive cells compared to collagen treatment alone. These data suggested that a collagen/heparin sulfate scaffold fabricated by a 3D bioprinter could enhance the mechanical properties of collagen and provide continuous guidance channels for axons, which would improve the neurological function after SCI. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1324-1332, 2017.