%0 Journal Article
%T The Neuroinflammatory Response in ALS: The Roles of Microglia and T Cells
%A Coral-Ann Lewis
%A John Manning
%A Fabio Rossi
%A Charles Krieger
%J Neurology Research International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/803701
%X Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by upper and lower motoneuron death. Mutations in the gene for superoxide dismutase 1 (SOD1) cause a familial form of ALS and have been used to develop transgenic mice which overexpress human mutant SOD1 (mSOD) and these mice exhibit a motoneuron disease which is pathologically and phenotypically similar to ALS. Neuroinflammation is a pathological hallmark of many neurodegenerative diseases including ALS and is typified by the activation and proliferation of microglia and the infiltration of T cells into the brain and spinal cord. Although the neuroinflammatory response has been considered a consequence of neuronal dysfunction and death, evidence indicates that manipulation of this response can alter disease progression. Previously viewed as deleterious to neuronal survival, recent reports suggest a trophic role for activated microglia in the mSOD mouse during the early stages of disease that is dependent on instructive signals from infiltrating T cells. However, at advanced stages of disease, activated microglia acquire increased neurotoxic potential, warranting further investigation into factors capable of skewing microglial activation towards a neurotrophic phenotype as a means of therapeutic intervention in ALS. 1. Introduction Neuroinflammation is a pathological hallmark of many neurodegenerative diseases including Alzheimer¡¯s disease (AD), Parkinson¡¯s disease (PD), and amyotrophic lateral sclerosis (ALS). It is characterized by the activation and proliferation of microglia (microgliosis) and the accumulation of infiltrating T lymphocytes at sites of neurodegeneration. Although often considered a consequence to neuronal injury and degeneration, the neuroinflammatory response can have protective or deleterious effects on neuronal survival. These disparate effects are elicited by the heterogeneous activation programs of microglia, which in turn are dictated by their surrounding microenvironment and by infiltrating T cells. 2. Amyotrophic Lateral Sclerosis and the mSOD Mouse Model Typically diagnosed during the fifth decade of life, amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motoneurons in the brainstem and spinal cord and loss of descending motor tracts. Clinical manifestations of ALS include muscle weakness, spasticity, muscle atrophy, and advancing paralysis that culminates in respiratory failure, the usual cause of death in affected patients. ALS is a disease primarily of sporadic etiology with a
%U http://www.hindawi.com/journals/nri/2012/803701/