Characterization of the microglia in three non-overlapping lysosomal storage diseases

Autor: antony cougnoux, Rebecca Drummond, Mason Fellmeth, Fatemeh Navid, Amanda Collar, James Iben, Niamh Cawley, Christopher Wassif, James Pickel, Ashok Kulkarni, Michail Lionakis, Forbes Porter
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:64.23-64.23
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.204.supp.64.23
Popis: Lysosomal storage diseases (LSDs) are a large family of inherited disorders characterized by abnormal endolysosomal accumulation of cellular material due to catabolic enzyme or transporter deficiencies. Depending on the affected metabolic pathway, these diseases manifest with somatic or central nervous system signs and symptoms. Neuroinflammation is a hallmark feature of LSDs with neurologic involvement such as mucolipidosis type IV (Mcoln1) or Niemann-Pick disease, type C1 (Npc1), but not Fabry disease (Gla). We investigated the properties of microglia from these three disorders using mouse models and a combination of flow cytometric, RNA sequencing, biochemical and immunofluorescence analyses. Stored material is present in the microglia of the different mice however only in Niemann-Pick disease, type C1 did we observe that neuroinflammation increases with disease progression. Fabry disease mice do not have neurological manifestation, and this is reflected by the minor changes in microglial properties. Lastly, mucolipidosis type IV mice have an early gliosis which decreases with disease progression. Comparison among microglia transcriptome profiles form these 3 diseases, and other disorders where transcriptome data is available, showed similarities with other neurodegenerative diseases. The phenotypic similarities between microglia from rare monogenic disorders, where the primary metabolic disturbance is known, and common neuroinflammatory diseases may provide novel insights for therapeutic intervention.
Databáze: OpenAIRE
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