Springer Science and Business Media LLC

Alzheimer’s disease (AD) is the leading cause of dementia. The majority of AD cases are late-onset, multifactorial cases. Genome-wide association studies have identified more than 30 loci associated with sporadic AD (SAD), one of which is Bridging integrator 1 (BIN1). For the past few years, there has been a consensus that BIN1 is second only to APOE as the strongest genetic risk factor for SAD. Therefore, many researchers have put great effort into studying the mechanism by which BIN1 might be involved in the pathogenetic process of AD. To date, plenty of evidence has shown that BIN1 may participate in several pathways in AD, including tau and amyloid pathology. In addition, BIN1 has been indicated to take part in other relevant pathways such as inflammation, apoptosis, and calcium homeostasis. In this review, we systemically summarize the research progress on how BIN1 participates in the development of AD, with the expectation of providing promising perspectives for future research.

Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. We sought to elucidate possible effects of phillyrin, an active constituent isolated from the Chinese medicinal herb Forsythia suspense, on hydrogen peroxide (H2O2)-induced cell death and determine the underlying molecular mechanisms in neuron-like PC12 cells. By MTT assay and lactate dehydrogenase (LDH) leakage assay, we found that phillyrin treatment effectively protected PC12 cells against H2O2-induced cell damage. H2O2 exposure induced oxidative stress in PC12 cells, as revealed by enhanced oxidative stress and decreased activities of antioxidative enzymes, which were inhibited by phillyrin pretreatment. ROS activated mitochondria-dependent apoptosis. The anti-apoptotic effects of phillyrin were also confirmed by acridine orange/ethidium bromide (AO/EB) staining. Mitochondrial membrane potential decrease, cytochrome c release, caspases activation, activation of AIF and Endo G were observed in H2O2-treated cells by rhodamine 123 or western blot. Interestingly, phillyrin effectively suppressed these changes. Moreover, phillyrin could inhibit H2O2-induced up-regulation of Bax/Bcl-2 ratio. In conclusion, phillyrin effectively inhibited H2O2-induced oxidative stress and apoptosis in PC12 cells.

Following the transection of peripheral sympathetic preganglionic axons comprising the cervical sympathetic trunk (CST), we observe robust glial and neuronal plasticity at 1 week post-injury in the rat spinal cord intermediolateral cell column (IML), which houses the injured parent neuronal cell bodies. This plasticity contributes to neuroprotection, as no neuronal loss in the IML is present at 16 weeks post-injury. Here, we administered the antibiotic minocycline or vehicle (VEH) daily for 1 week after CST transection to investigate the role of activated microglia in IML glial and neuronal plasticity and subsequent neuronal survival. At 1 week post-injury, minocycline treatment did not alter microglia number in the IML, but led to a dampened microglia activation state. In addition, the increases in oligodendrocyte (OL) lineage cells and activated astrocytes following injury in VEH rats were attenuated in the minocycline-treated rats. Further, the normal downregulation of choline acetyltransferase (ChAT) in the injured neurons was blunted. At 16 weeks post-injury, fewer ChAT+ neurons were present in the minocycline-treated rats, suggesting that activated microglia together with the glial and neuronal plasticity at 1 week post-injury contribute to the long-term survival of the injured neurons. These results provide evidence for beneficial crosstalk between activated microglia and neurons as well as other glial cells in the cord following peripheral axon injury, which ultimately leads to neuroprotection. The influences of microglia activation in promoting neuronal survival should be considered when developing therapies to administer minocycline for the treatment of neurological pathologies.

MicroRNAs can function as oncogenes or tumor suppressors in glioma. Previously, we showed that miR-107 inhibits glioma cell proliferation, migration, and invasion. Since tumor growth and invasion are closely related to angiogenesis, we further examined the role of miR-107 in glioma angiogenesis. In a co-culture of glioma cells and human brain microvascular endothelial cells (HBMVEC), overexpression of miR-107 in glioma cells led to the inhibition of HBMVEC proliferation, migration, and tube formation ability. ELISA, RT-PCR, and western blot assays revealed that upregulation of miR-107 in glioma cells inhibits VEGF expression. Our findings collectively support the critical involvement of miR-107 in glioma cell angiogenesis and highlight its potential as a therapeutic target for glioma.

Silent information regulator factor 2-related enzyme 1 (sirtuin 1, Sirt1) is a nicotinamide adenine dinucleotide-dependent deacetylase, which can deacetylate histone and non-histone proteins and other transcription factors, and is involved in the regulation of many physiological functions, including cell senescence, gene transcription, energy balance, and oxidative stress. Ischemia/hypoxia injury remains an unresolved and complicated situation in the diseases of ischemia stroke, heart failure, and coronary heart disease, especially among the old folks. Studies have demonstrated that aging could enhance the vulnerability of brain, heart, lung, liver, and kidney to ischemia/hypoxia injury and the susceptibility in old folks to ischemia/hypoxia injury might be associated with Sirt1. In this review, we mainly summarize the role of Sirt1 in modulating pathways against energy depletion and its involvement in oxidative stress, apoptosis, and inflammation under the condition of ischemia/hypoxia.