Ferritin is closely associated with microglia in amyotrophic lateral sclerosis.

Autor:	Gao J; Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, United States., Okolo O; Department of Pathology, Case Western Reserve University, Cleveland, OH, United States., Siedlak SL; Department of Pathology, Case Western Reserve University, Cleveland, OH, United States., Friedland RP; Department of Neurology, University of Louisville, Louisville, KY, United States., Wang X; Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, United States.; Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.
Jazyk:	angličtina
Zdroj:	Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2024 Nov 01; Vol. 83 (11), pp. 917-926.
DOI:	10.1093/jnen/nlae074
Abstrakt:	Iron deposition is a hallmark of amyotrophic lateral sclerosis (ALS) and has been strongly implicated in its pathogenesis. As a byproduct of cellular oxidative stress, iron dysregulation modifies basal levels of the regulatory iron-binding protein ferritin. Examination of thoracic and lumbar spinal cord tissues found increased ferritin immunostaining in white matter axons that corresponded to areas of increased microgliosis in 8 ALS patients versus 8 normal subjects. Gray matter areas containing the motor neurons also demonstrated increased ferritin and microglia in ALS compared to controls but at lower levels than in the white matter. Motor neurons with or without TDP-43 inclusions did not demonstrate either increased ferritin or associated microglial activation. We also observed an association of ferritin with microglia in cerebral cortical tissue samples of ALS cases and in the spinal cord tissues of transgenic mice expressing the SOD1G93A mutation. Elevated ferritin levels were detected in the insoluble fraction from spinal cord tissues of individuals with ALS. These findings suggest that activated microglia and increased ferritin may play significant roles in ALS progression since they are found closely associated in areas of axonal and cortical degeneration. (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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