English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Amyotrophic lateral sclerosis (ALS) is a devastating fatal motor neuron disease, for which there is currently no cure or effective treatment. In this disease, local neuroinflammation develops along the disease course and contributes to its rapid progression. In several models of CNS pathologies, circulating immune cells were shown to display an indispensable role in the resolution of the neuroinflammatory response. The recruitment of such cells to the CNS involves activation of the choroid plexus (CP) of the brain for leukocyte trafficking, through a mechanism that requires IFN-γ signaling. Here, we found that in the mutant SOD1(G93A) (mSOD1) mouse model of ALS, the CP does not support leukocyte trafficking during disease progression, due to a local reduction in IFN-γ levels. Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma. The immunization resulted in the attenuation of disease progression and an increased life expectancy of the mSOD1 mice. Collectively, our results demonstrate that recruitment of immunoregulatory cells to the diseased spinal cord in ALS, needed for fighting off the pathology, can be enhanced by transiently boosting peripheral immunity to myelin antigens.

the journal of neuroscience/the journal of neuroscience

Immunization with a Myelin-Derived Antigen Activates the Brain's Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS