Microglia Influence Neurofilament Deposition in ALS iPSC-Derived Motor Neurons.

Autor:	Allison RL; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Adelman JW; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Abrudan J; Genomic Science and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, WI 53226, USA., Urrutia RA; Genomic Science and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Division of Research, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Zimmermann MT; Genomic Science and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Clinical and Translational Sciences Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Mathison AJ; Genomic Science and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Division of Research, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Ebert AD; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2022 Jan 27; Vol. 13 (2). Date of Electronic Publication: 2022 Jan 27.
DOI:	10.3390/genes13020241
Abstrakt:	Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motor neuron loss is the primary phenotype, leading to muscle weakness and wasting, respiratory failure, and death. Although a portion of ALS cases are linked to one of over 50 unique genes, the vast majority of cases are sporadic in nature. However, the mechanisms underlying the motor neuron loss in either familial or sporadic ALS are not entirely clear. Here, we used induced pluripotent stem cells derived from a set of identical twin brothers discordant for ALS to assess the role of astrocytes and microglia on the expression and accumulation of neurofilament proteins in motor neurons. We found that motor neurons derived from the affected twin which exhibited increased transcript levels of all three neurofilament isoforms and increased expression of phosphorylated neurofilament puncta. We further found that treatment of the motor neurons with astrocyte-conditioned medium and microglial-conditioned medium significantly impacted neurofilament deposition. Together, these data suggest that glial-secreted factors can alter neurofilament pathology in ALS iPSC-derived motor neurons.
Databáze:	MEDLINE
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