Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies

Publication date: February 2019Source: The Lancet Neurology, Volume 18, Issue 2Author(s): David R Beers, Stanley H AppelSummaryNeuroinflammation is a common pathological feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and is characterised by activated CNS microglia and astroglia, proinflammatory peripheral lymphocytes, and macrophages. Data from clinical studies show that multiple genetic mutations linked to ALS (eg, mutations in SOD1, TARDBP, and C9orf72) enhance this neuroinflammation, which provides compelling evidence for immune dysregulation in the pathogenesis of ALS. Transgenic rodent models expressing these mutations induce an ALS-like disease with accompanying inflammatory responses, confirming the immune system's involvement in disease progression. Even in the absence of known genetic alterations, immune dysregulation has been shown to lead to dysfunctional regulatory T lymphocytes and increased proinflammatory macrophages in clinical studies. Therefore, an improved understanding of the biological processes that induce this immune dysregulation will help to identify therapeutic strategies that circumvent or ameliorate the pathogenesis of ALS. Emerging cell-based therapies hold the promise of accomplishing this goal and, therefore, improving quality of life and extending survival in patients with ALS.

Source: The Lancet Neurology - January 20, 2019 Category: Neurology Source Type: research