PD-Like Pathogenesis in Caenorhabditis elegans Intestinally Infected with Nocardia farcinica and the Underlying Molecular Mechanisms.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the abnormal aggregation of α-synuclein (α-syn) and the loss of dopaminergic neurons. Although microbial infection has been implicated in the pathogenesis of PD, the associated virulence factors and the underlying molecular mechanisms require further elucidation. Here, we found that intestinal infection with Nocardia farcinica induced a series of PD-like symptoms in Caenorhabditis elegans, such as the accelerated degeneration of dopaminergic neurons, impaired locomotion capacity, and enhanced α-syn aggregation, through the disturbance of mitochondrial functions. To identify the potential virulence factors involved in these effects, we knocked out the nbtB/C and nbtS genes in N. farcinica, which are localized in the gene clusters responsible for nocobactin biosynthesis. The deletion of either gene partially rescued the degenerative effects of wild-type N. farcinica on dopaminergic neurons by attenuating mitochondrial dysfunction. LC-MS analysis further identified a decrease in the abundance of several siderophores in the two mutants, including nocobactin NA-a, nocobactin NA-b, and nocardimicin B. Collectively, our results demonstrated that intestinal N. farcinica infection in C. elegans facilitates PD-like pathogenesis and provides novel evidence for the involvement of pathogenic bacteria in neurodegenerative diseases via non-neuroinvasive mechanisms.

Role and molecular regulatory mechanisms of Hippo signaling pathway in Caenorhabditis elegans and mammalian cell models of Alzheimer's disease.

Although there is increasing evidence for the involvement of Hippo signaling in Alzheimer's disease (AD), the detailed functions and regulatory mechanisms are not fully understood, given the diverse biological effects of this pathway. In the present work, we used Caenorhabditis elegans and mammalian cell models to investigate changes in the Hippo signaling pathway in response to Aß and the downstream effects on AD development. Aß1-42 production in the AD models decreased phosphorylation of the upstream CST-1/WTS-1 kinase cascade and promoted an interaction between LIN-10 and YAP-1, leading to the nuclear translocation of YAP-1 and inducing gene transcription in conjunction with the transcription factor EGL-44. The YAP-1/EGL-44 complex suppressed the autophagy-lysosome pathway by modulating mTOR signaling, which enhanced Aß1-42 accumulation and promoted AD progression. These results demonstrate for the first time that crosstalk between Hippo and mTOR signaling contributes to AD development by enhancing Aß production, resulting in inhibition of Hippo signaling and autophagy-lysosome pathway and Aß accumulation, suggesting potential therapeutic targets for the treatment or prevention of AD.

Novel Genes and Key Signaling Molecules Involved in the Repulsive Response of Meloidogyne incognita against Biocontrol Bacteria.

The ability of the model organism, Caenorhabditis elegans, to distinguish and escape from pathogenic bacteria has been extensively studied; however, studies on the repulsive response of Meloidogyne incognita are still in their infancy. We have recently demonstrated that biocontrol bacteria induce a repulsive response in M. incognita via two classical signaling pathways. The present study aimed to identify the novel genes and signaling molecules of M. incognita that potentially contribute to its defense reaction. Analysis of the transcriptome data of M. incognita with and without a repulsive response against Bacillus nematocida B16 obtained 15 candidate genes, of which the novel genes Minc3s01748g26034 and Minc3s02548g30585 were found to regulate the aversive behavior of M. incognita, and their functions were further validated. To further confirm the neuronal localization of the two novel genes in M. incognita, in situ hybridization was conducted using the digoxin-labeled probes of ten tag genes, and preferentially profiled the localization of amphid sensory neurons of M. incognita. Analysis of the overviewed neuronal map suggested that Minc3s01748g26034 and Minc3s02548g30585 functioned in ASK/ASI and CEPD/V neurons, respectively. During their interactions, the volatile compounds 3-methyl-butyric acid and 2-methyl-butyric acid produced by the biocontrol bacteria were predicted as the primary signaling molecules that promoted the repulsive behavior of M. incognita against biocontrol bacteria. The findings provided novel insights into the mechanisms underlying the repulsive response of M. incognita that are different from the canonical molecular pathways previously found in C. elegans and can aid in developing novel strategies for controlling root-knot nematodes.