Alzheimer’s disease (AD) is an incurable neurodegenerative disease. Numerous studies have demonstrated a critical role for dysregulated glucose metabolism in its pathogenesis. In this review, we summarize metabolic alterations in aging brain and AD-related metabolic deficits associated with glucose metabolism dysregulation, glycolysis dysfunction, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) deficits, and pentose phosphate pathway impairment. Additionally, we discuss recent treatment strategies targeting metabolic defects in AD, including their limitations, in an effort to encourage the development of novel therapeutic strategies.

The Drp1-HK1-NLRP3 axis is a key mechanism of oligodendrocyte damage and white matter degeneration in AD.

Polyetheretherketone (PEEK) has been widely applied in fixed dental prostheses, comprising crowns, fixed partial dentures, and post-and-core. PEEK’s excellent mechanical properties facilitate better stress distribution than conventional materials, protecting the abutment teeth. However, the stiffness of PEEK is not sufficient, which can be improved via fiber reinforcement. PEEK is biocompatible. It is nonmutagenic, noncytotoxic, and nonallergenic. However, the chemical stability of PEEK is a double-edged sword. On the one hand, PEEK is nondegradable and intraoral corrosion is minimized. On the other hand, the inert surface makes adhesive bonding difficult. Numerous strategies for improving the adhesive properties of PEEK have been explored, including acid etching, plasma treatment, airborne particle abrasion, laser treatment, and adhesive systems.

Mitochondria are organelles responsible for bioenergetic metabolism, calcium homeostasis, and signal transmission essential for neurons due to their high energy consumption. Accumulating evidence has demonstrated that mitochondria play a key role in axon degeneration and regeneration under physiological and pathological conditions. Mitochondrial dysfunction occurs at an early stage of axon degeneration and involves oxidative stress, energy deficiency, imbalance of mitochondrial dynamics, defects in mitochondrial transport, and mitophagy dysregulation. The restoration of these defective mitochondria by enhancing mitochondrial transport, clearance of reactive oxidative species (ROS), and improving bioenergetic can greatly contribute to axon regeneration. In this paper, we focus on the biological behavior of axonal mitochondria in aging, injury (e.g., traumatic brain and spinal cord injury), and neurodegenerative diseases (Alzheimer's disease, AD; Parkinson's disease, PD; Amyotrophic lateral sclerosis, ALS) and consider the role of mitochondria in axon regeneration. We also compare the behavior of mitochondria in different diseases and outline novel therapeutic strategies for addressing abnormal mitochondrial biological behavior to promote axonal regeneration in neurological diseases and injuries.

Metformin has been reported to function as the anti-tumor inhibiting the growth of different types of cancers, including bladder cancer. But there are few reports on the roles of Yap1, the key molecule of Hippo pathway, in the metformin induced inhibition of bladder cancer (BLCA). We are wondering if the inhibitory effect of metformin on bladder cancer is fulfilled via Yap1 and exploring the related mechanism. MTS and colony formation assays were used to explore the cellular viabilities and proliferation of BLCA cells challenged by metformin at different concentrations, in vitro. Flow Cytometry (FCM) was used to analyze the cell cycle and the cellular apoptosis of the BLCA cells. Western Blot was performed to detect the expressions of AMPKα, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines. RNAi method was used for the related genetic functional analysis. The relationships among Yap1, TEADs and CCNE1/2 were predicted and evaluated using bioinformatics, dual-luciferase reporter and co-immunoprecipitation (Co-IP) assays. For in vivo experiments, a xenograft model was used to investigate the effects of metformin on the proliferation of BLCA cells. And Immunohistochemistry (IHC) assay was performed to assess the expressions of CCNE1/2 and Yap1 proteins in the tumor tissues from the model. Metformin could inhibit the proliferation of the BLCA cells via inducing the G1 cell cycle arrest without apoptosis. And metformin upregulated the phosphorylated AMPKα and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6. AMPK inhibition by compound C (CC) restored the cell proliferation and the G1 cell cycle arrest induced by metformin, in vivo. Knockdown of YAP1 inhibited the proliferation of BLCA cells and caused the cell cycle arrest at G1 phase by decreasing the expressions of CCNE1/2 and other G1 phase related molecules, which has been restored by the Yap 5SA mutant. Bioinformatics analysis showed that trans-factor TEAD4 was highly expressed and positively associated with the expressions of CCNE1 and CCNE2 in BLCA and only TEAD4 was precipitated by Yap1 in the BLCA cells. Further studies demonstrated that Yap1 positively regulated both CCNE1 and CCNE2 expressions via forming complex with TEAD4. Furthermore, we observed that metformin inhibited the cell proliferation by decreasing the expressions of Yap1 and both CCNE1 and CCNE2 in xenograft model. The results of our study reveal a new potential regulatory pathway in which metformin inhibits cell proliferation via AMPKα/Yap1/TEAD4/CCNE1/2 axis in BLCA cells, providing new insights into novel molecular therapeutic targets for BLCA.

Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are characterized by a progressive loss of selective neuron subtypes in the central nervous system (CNS). Although various factors account for the initiation and development of these diseases, accumulating evidence shows that impaired mitochondrial function is a prominent and common mechanism. Mitochondria play a critical role in neurons and are involved in energy production, cellular metabolism regulation, intracellular calcium homeostasis, immune responses, and cell fate. Thus, cells in the CNS heavily rely on mitochondrial integrity. Many aspects of mitochondrial dysfunction are manifested in neurodegenerative diseases, including aberrant mitochondrial quality control (mitoQC), mitochondrial-driven inflammation, and bioenergetic defects. Herein, we briefly summarize the molecular basis of mitoQC, including mitochondrial proteostasis, biogenesis, dynamics, and organelle degradation. We also focus on the research, to date, regarding aberrant mitoQC and mitochondrial-driven inflammation in several common neurodegenerative diseases. In addition, we outline novel therapeutic strategies that target aberrant mitoQC in neurodegenerative diseases.