How are necroptosis, immune dysfunction, and motoneuron death connected in amyotrophic lateral sclerosis?

Abstract

How to cite this article: Liu JF, Zheng OX, Xin JG, Chen HH, Xin JJ. How are necroptosis, immune dysfunction, and motoneuron death connected in amyotrophic lateral sclerosis ? Neuroimmunol Neuroinflammation 2017;4:109-16. Abnormal immune response/inflammation is present in patients of amyotrophic lateral sclerosis (ALS). Autoimmune-related inflammation has been thought to be involved in the pathogenesis of ALS. However, how the abnormal immune responses are initiated, what specific immune cells and how these immune cells are involved in this disease have not been well understood. This is partly owing to two facts of ALS: late diagnosis and chronic nature. The late diagnosis makes it difficult to conclude whether the abnormal immune responses/inflammation is the cause or result of the disease. The chronic nature makes it difficult to determine the best timing for the detection of such autoimmune responses. To resolve these two challenges for research, the authors introduced motor nerve injury (facial nerve axotomy, FNA) into a pre-symptomatic mouse ALS model (8-week-old SOD1 G93A mice), which induces a readily detectable immune response in a predictable time period (3-14 days). The authors found that pre-symptomatic SOD1 G93A mice showed a higher basal level of T cell activation and Th17 cells than WT mice, which can be further increased by FNA. However, why these pro-inflammatory Th lymphocyte MinireviewThis is an open access article distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

A Combination of Intrathecal and Intramuscular Application of Human Mesenchymal Stem Cells Partly Reduces the Activation of Necroptosis in the Spinal Cord of SOD1G93A Rats

“…The pro‐inflammatory factor NF‐κB mediates the inflammation reaction via TNF‐α and other inflammatory cytokines . Its activation determines the pro‐inflammatory phenotype of microglial cells in ALS , whereas its inhibition can slow down disease progression .…”

Peripheral proinflammatory Th1/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis

“…T helper 17 (Th17) cells and regulatory T cells (Treg) are a subset of CD4+ T cells recently caught more attention which play an important role in promoting (Th17) or suppressing (Treg) inflammation and are crucial in the development of different autoimmune diseases, such as multiple sclerosis 3,24,25 . Treg cells were inversely correlated with progression rates in ALS patients and the transfer of endogenous Treg cells of ALS mice from early disease stages into ALS mice lengthen disease duration and prolong survival, suggesting a neuroprotective function of these cells in ALS 26,27 .…”

“…One hypothesis is therefore that due to MN injury, MN specific antigens are released and processed by antigen-presenting cells (APC; e.g. monocytes or dendritic cells) inducing priming of specific Th17 cells and their recruitment into the CNS, which promote a MN-specific inflammation leading to MN death 3 . So far only one study was investigating Th17 cells in the blood of ALS patients, showing an increase of this immune cell population in ALS patients 25 .…”