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

Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2004-

Amyotrophic Lateral Sclerosis*/genetics ; Disease Progression* ; Gene-Environment Interaction*; Animals ; Humans

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.

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Keywords: Inhibition of neuregulin-mediated inflammation; Nerve injury-mediated neuroinflammation; Neuronal-glial communication through glial growth factor neuregulin

Date Created: 20200608 Date Completed: 20210331 Latest Revision: 20231111

20250114

PMC7276078

10.1186/s12974-020-01849-7

32505190