Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment.

Abstract:

:Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease affecting the neuromuscular system. While there have been a number of important genetic discoveries, there are no therapeutics capable of stopping its insidious progression. Lessons from clinical histories reveal that ALS can start focally at a single limb, but then segmentally spread up and down the spinal cord as well as in the motor cortex and cortex of frontal and temporal lobes until respiratory muscles fail. With or without a clear genetic etiology, often there is no explanation as to why it starts in one region of the body versus another. Similarly, once the disease starts the mechanisms by which the neurodegenerative process spreads are not known. Here, we summarize recent work in animal models that support the hypothesis that critical environmental contributions, such as a nerve injury, can initiate the disease process. We also propose that pathological axoglial signaling by the glial growth factor neuregulin-1 leads to the slow propagation of neuroinflammation resulting in neurodegeneration up and down the spinal cord and that locally applied drugs that block neuregulin-1 signaling could slow or halt the spread of disease.

journal_name

J Neuroinflammation

authors

Schram S,Loeb JA,Song F

doi

10.1186/s12974-020-01849-7

subject

Has Abstract

pub_date

2020-06-06 00:00:00

pages

175

issue

1

issn

1742-2094

pii

10.1186/s12974-020-01849-7

journal_volume

17

pub_type

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