No abstract

No abstract

No abstract

No abstract

Beta amyloid (Aβ) is well accepted to play a central role in the pathogenesis of Alzheimer’s disease (AD). The present work evaluated the therapeutic effects of low-level laser irradiation (LLI) on Aβ-induced neurotoxicity in rat hippocampus. Aβ 1–42 was injected bilaterally to the hippocampus CA1 region of adult male rats, and 2-minute daily LLI treatment was applied transcranially after Aβ injection for 5 consecutive days. LLI treatment suppressed Aβ-induced hippocampal neurodegeneration and long-term spatial and recognition memory impairments. Molecular studies revealed that LLI treatment: (1) restored mitochondrial dynamics, by altering fission and fusion protein levels thereby suppressing Aβ-induced extensive fragmentation; (2) suppressed Aβ-induced collapse of mitochondrial membrane potential; (3) reduced oxidized mitochondrial DNA and excessive mitophagy; (4) facilitated mitochondrial homeostasis via modulation of the Bcl-2-associated X protein/B-cell lymphoma 2 ratio and of mitochondrial anti-oxidant expression; (5) promoted cytochrome c oxidase activity and adenosine triphosphate synthesis; (6) suppressed Aβ-induced glucose-6-phosphate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activity; (7) enhanced the total antioxidant capacity of hippocampal CA1 neurons, whereas reduced the oxidative damage; and (8) suppressed Aβ-induced reactive gliosis, inflammation, and tau hyperphosphorylation. Although development of AD treatments has focused on reducing cerebral Aβ levels, by the time the clinical diagnosis of AD or mild cognitive impairment is made, the brain is likely to have already been exposed to years of elevated Aβ levels with dire consequences for multiple cellular pathways. By alleviating a broad spectrum of Aβ-induced pathology that includes mitochondrial dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, and tau pathology, LLI could represent a new promising therapeutic strategy for AD.

Exercise pretraining exerts multifactorial benefits on AD that support its use as a promising new therapeutic option for prevention of neurodegeneration in the elderly and/or AD population.

Liquid biopsy enables noninvasive and dynamic analysis of molecular or cellular biomarkers, and therefore holds great potential for the diagnosis, prognosis, monitoring of disease progress and treatment efficacy, understanding of disease mechanisms, and identification of therapeutic targets for drug development. In this review, the recent progress in nanomaterials, nanostructures, nanodevices, and nanosensors for liquid biopsy is summarized, with a focus on the detection and molecular characterization of circulating tumor cells (CTCs) and extracellular vesicles (EVs). The developments and advances of nanomaterials and nanostructures in enhancing the sensitivity, specificity, and purity for the detection of CTCs and EVs are discussed. Sensing techniques for signal transduction and amplification as well as visualization strategies are also discussed. New technologies for the reversible release of the isolated CTCs and EVs and for single‐CTC/EV analysis are summarized. Emerging microfluidic platforms for the integral on‐chip isolation, detection, and molecular analysis are also included. The opportunities, challenges, and prospects of these innovative materials and technologies, especially with regard to their feasibility in clinical applications, are discussed. The applications of nanotechnology‐based liquid biopsy will bring new insight into the clinical practice in monitoring and treatment of tumor and other significant diseases.

Priming of synaptic vesicles involves Munc13‐catalyzed transition of the Munc18‐1/syntaxin‐1 complex to the SNARE complex in the presence of SNAP‐25 and synaptobrevin‐2; Munc13 drives opening of syntaxin‐1 via the MUN domain while Munc18‐1 primes SNARE assembly via domain 3a. However, the underlying mechanism remains unclear. In this study, we have identified a number of residues in domain 3a of Munc18‐1 that are crucial for Munc13 and Munc18‐1 actions in SNARE complex assembly and synaptic vesicle priming. Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18‐1/syntaxin‐1 complex and the MUN domain. This interaction enables the MUN domain to drive the opening of syntaxin‐1 linker region, thereby leading to the extension of domain 3a and promoting synaptobrevin‐2 binding. In addition, we identified two residues (K332/K333) at the bottom of domain 3a that mediate the interaction between Munc18‐1 and the SNARE motif of syntaxin‐1. This interaction ensures Munc18‐1 to persistently associate with syntaxin‐1 during the conformational change of syntaxin‐1 from closed to open, which reinforces the role of Munc18‐1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18‐1/syntaxin‐1 complex and enables Munc18‐1 to prime SNARE assembly.