Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis

Abstract

The central nervous system (CNS) is equipped with a variety of cell types, all of which are assigned particular roles during the development, maintenance, function and repair of neural tissue. One glial cell type, microglia, deserves particular attention, as its role in the healthy or injured CNS is incompletely understood. Evidence exists for both regenerative and degenerative functions of these glial cells during neuronal injury. This review integrates the current knowledge of the role of microglia in an adult-onset neurodegenerative disease, amyotrophic lateral sclerosis (ALS), and pays particular attention to the possible mechanisms of initiation and propagation of neuronal damage during disease onset and progression. Microglial cell properties, behavior and detected inflammatory reactions during the course of the disease are described. The neuroinflammatory changes that occur in a mouse model of ALS are summarized. The understanding of microglial function in the healthy and injured CNS could offer better diagnostic as well as therapeutic approaches for prevention, retardation, or repair of neural tissue degeneration.

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

“…Whether such events occur in sequence, in tandem, or transiently are not yet known. Indeed, there is considerable controversy in the experimental literature about the relative roles of astrocytes and microglia in neurodegeneration (Sargsyan et al 2005). …”

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

“…injurious pathways occurring peripherally at the neuromuscular junction and centrally at the cell body of the motor neuron [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Histopatholgy in the animal model reveals a disruption at the neuromuscular junction that appears first followed by a "dying back" of the axon [25].…”

Strategic approaches to developing drug treatments for ALS

“…One underlying theme emerging from these and other studies provides evidence for distinct phases of ALS -onset and early stages, symptomatic and end stages -and dynamic contributions of motor neurons and glia throughout these stages [53,54]. These complex interactions between motor neurons and glia make cell type selection a critical consideration when designing mechanistic and intervention studies.…”