targeted-knockdown-of-genes-in-the-choroid-plexus

Targeted Knockdown of Genes in the Choroid Plexus

The choroid plexus (ChP) serves as a critical gateway for immune cell infiltration into the central nervous system (CNS) under both physiological and ...

The Second Affiliated Hospital of Wenzhou Medical University

Wenzhou Medical University

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). IFN-gamma (IFN-γ), a critically important immunomodulator, has been widely studied in MS pathology. The confusing and complex effects of IFN-γ in MS patients and rodent models, however, cause us to look more closely at its exact role in MS. In this study, we identified the role of the IFN-γ signaling in the choroid plexus (CP) in the experimental autoimmune encephalomyelitis (EAE) model. We found that the IFN-γ signal was rapidly amplified when CNS immune cell infiltration occurred in the CP during the progressive stage. Furthermore, using two CP-specific knockdown strategies, we demonstrated that blocking the IFN-γ signal via knockdown of IFN-γR1 in the CP could protect mice against EAE pathology, as evidenced by improvements in clinical scores and infiltration. Notably, knocking down IFN-γR1 in the CP reduced the local expression of adhesion molecules and chemokines. This finding suggests that IFN-γ signaling in the CP may participate in the pathological process of EAE by preventing pathological T helper (Th) 17 cells from infiltrating into the CNS. Finally, we showed that the unbalanced state of IFN-γ signaling between peripheral lymphocytes and the choroid plexus may determine whether IFN-γ has a protective or aggravating effect on EAE pathology. Above all, we discovered that IFN-γR1-mediated IFN-γ signaling in the CP was a vital pathway in the pathological process of EAE.

Blocking the IFN-gamma signal in the choroid plexus confers resistance to experimental autoimmune encephalomyelitis.

It has been found that the main cause of neurodegenerative proteinopathies, especially Alzheimer's disease (AD) is the formation of Aβ amyloid plaques, which can be regulated by application of potential small molecules. In the present study, we aimed to investigate the inhibitory effect of danshensu on Aβ(1-42) aggregation and relevant apoptotic pathway in neurons. A broad range of spectroscopic, theoretical, and cellular assays were done to investigate the anti-amyloidogenic characteristics of danshensu. It was found that danshensu triggers its inhibitory effect against Aβ(1-42) aggregation through modulation of hydrophobic patches as well as structural and morphological changes through a stacking interaction. Furthermore, it was observed that incubation of Aβ(1-42) samples with danshensu during aggregation process recovered the cell viability and mitigated the expression of caspase-3 mRNA and protein as well caspase-3 activity deregulated by Aβ(1-42) amyloid fibrils alone. In general, obtained data showed that danshensu potentially inhibits Aβ(1-42) aggregation and associated proteinopathies through regulation of apoptotic pathway in a concentration-dependent manner. Therefore, danshensu may be used as a promising biomolecule against the Aβ aggregation and associated proteinopathies, which can be further analyzed in the future studies for the treatment of AD.

Article	Year
Blocking the IFN-gamma signal in the choroid plexus confers resistance to experimental autoimmune encephalomyelitis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 36921064	2023
Danshensu inhibits Aβ aggregation and neurotoxicity as one of the main prominent features of Alzheimer's disease. International journal of biological macromolecules\| PubMed ID: 37315666	2023

Haiyan Lin

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