Title
Increased axonal ribosome numbers is an early event in the pathogenesis of amyotrophic lateral sclerosisIncreased axonal ribosome numbers is an early event in the pathogenesis of amyotrophic lateral sclerosis
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO)
Publication type
article
Publication
Subject
Engineering sciences. Technology
Source (journal)
PLoS ONE
Volume/pages
9(2014):1, p. 1-7
ISSN
1932-6203
Article Reference
e87255
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Myelinating glia cells support axon survival and functions through mechanisms independent of myelination, and their dysfunction leads to axonal degeneration in several diseases. In amyotrophic lateral sclerosis (ALS), spinal motor neurons undergo retrograde degeneration, and slowing of axonal transport is an early event that in ALS mutant mice occurs well before motor neuron degeneration. Interestingly, in familial forms of ALS, Schwann cells have been proposed to slow disease progression. We demonstrated previously that Schwann cells transfer polyribosomes to diseased and regenerating axons, a possible rescue mechanism for disease-induced reductions in axonal proteins. Here, we investigated whether elevated levels of axonal ribosomes are also found in ALS, by analysis of a superoxide dismutase 1 (SOD1)(G93A) mouse model for human familial ALS and a patient suffering from sporadic ALS. In both cases, we found that the disorder was associated with an increase in the population of axonal ribosomes in myelinated axons. Importantly, in SOD1(G93A) mice, the appearance of axonal ribosomes preceded the manifestation of behavioral symptoms, indicating that upregulation of axonal ribosomes occurs early in the pathogenesis of ALS. In line with our previous studies, electron microscopy analysis showed that Schwann cells might serve as a source of axonal ribosomes in the disease-compromised axons. The early appearance of axonal ribosomes indicates an involvement of Schwann cells early in ALS neuropathology, and may serve as an early marker for disease-affected axons, not only in ALS, but also for other central and peripheral neurodegenerative disorders.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/44ffc1/7069.pdf
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