Translocator Protein Ligand Protects against Neurodegeneration in the MPTP Mouse Model of Parkinsonism

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jing GongAnja Schneider

Abstract

Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease. Parkinson's disease is a movement disorder with characteristic motor features that arise due to the loss of dopaminergic neurons from the substantia nigra. Although symptomatic treatment by the dopamine precursor levodopa and dopamine agonists can improve motor symptoms, no disease-modifying therapy exists yet. Here, we show that Emapunil (AC-5216, XBD-173), a synthetic ligand of the translocator protein 18, ameliorates degeneration of dopaminergic neurons, preserves striatal dopamine metabolism, and prevents motor dysfunction in female mice treated with the MPTP, as a model of parkinsonism. We found that Emapunil modulates the inositol requiring kinase 1α (IRE α)/X-box binding protein 1 (XBP1) unfolded protein response pathway and induces a shift from pro-inflammatory toward anti-inflammatory microglia activation. Previously, Emapunil was shown to cross the blood-brain barrier and to be safe and well tolerated in a Phase II clinical trial. Therefore, our data suggest that Emapunil may be a promising approach in the treatment of Parkinson's disease.SIGNIFICANCE STATEMENT Our study reveals a beneficial effect of Emapunil on dopami...Continue Reading

Citations

Mar 19, 2020·Neuropsychiatric Disease and Treatment·Shanshan HuJianghui Dong
Jun 3, 2020·Nature Communications·Anne WolfThomas Langmann
Jun 26, 2020·Frontiers in Aging Neuroscience·Sara BelloliMaria Carla Gilardi
Feb 18, 2020·Current Alzheimer Research·Marianna E Jung
Jul 10, 2019·Pharmacology & Therapeutics·Marie-Christine TononJérôme Leprince
Jan 13, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Erik NutmaBenjamin B Tournier
Jan 2, 2021·International Journal of Molecular Sciences·Jinjiang Fan, Vassilios Papadopoulos
Mar 6, 2021·Molecular Psychiatry·Michele FrisonMichelangelo Campanella
May 11, 2020·Biochemical Pharmacology·Barbara CostaClaudia Martini
Mar 16, 2021·Frontiers in Immunology·Lauren H FairleyAnna M Barron
Mar 21, 2021·Journal of Neuroinflammation·Lauren H FairleyAnna M Barron
Dec 24, 2020·European Biophysics Journal : EBJ·Gwladys RivièreMarkus Zweckstetter
Aug 4, 2021·Open Biology·Joshua Wang, Kate Beecher

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