Astrocytes and Microglia as Non-cell Autonomous Players in the Pathogenesis of ALS

Lee, Jung‐Hee; Hyeon, Seung Jae; Im, Hyeonjoo; Ryu, Hwa-Sung; Kim, Yunha; Ryu, Hoon

doi:10.5607/en.2016.25.5.233

Cited by 124 publications

(111 citation statements)

References 59 publications

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“…Accumulating evidence suggests that activated microglia may contribute to ALS, a degenerative disorders characterized by the loss of SMN. [33] The presence of spinal arteriolosclerosis in the current cases in the absence of microinfarcts suggests that age-related loss of spinal motor neurons may be due not to ischemic damage which is common in the cerebrum but to other mechanisms. The association of activated microglia with SMN counts in the current study lends support to the idea that inflammation in the absence of microscopic infarcts might nonetheless contribute to loss of SMN in older adults.…”

Section: Discussionmentioning

confidence: 89%

“…Recent studies suggest a role for microglia in the loss of spinal motor neurons in motor neuron disease. [33] Therefore, in a subset of cases we obtained activated spinal microglia counts in the ventral horns where from which we obtained spinal motor neuron indices. Then we examined the relationship of SMN indices with the level of motor function proximate to death.…”

Section: Introductionmentioning

confidence: 99%

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Spinal motor neurons and motor function in older adults

et al. 2018

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This study examined the relation of lumbar spinal motor neuron (SMN) indices and motor function proximate to death in community-dwelling older adults. Older adults (N=145) participating in the Rush Memory and Aging Project underwent structured clinical testing proximate to death and brain and spinal cord autopsy at time of death. Ten motor performances were summarized by a composite global motor score. Choline acetyltransferase immunostaining was used to identify spinal motor neurons of the L4/5 segment. SMN counts and area and ventral horn area were collected. Linear regression modeling showed that the association of SMN counts and density with global motor scores proximate to death varied with sex. Separate models in men and women showed that this significant interaction was due to the association of higher SMN counts and density with higher global motor scores proximate to death in men but not women. These associations were unchanged when we controlled for indices of brain pathologies or chronic health conditions. In 38 cases with counts of activated microglia available, higher counts of activated microglia were associated with lower SMN counts. Activated spinal microglia and loss of spinal motor neurons may contribute to motor impairments in older men.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Spinal motor neurons and motor function in older adults

et al. 2018

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“…Failure to maintain appropriate levels of glutamate can cause excitotoxicity. It is thought that excitotoxicity may contribute to motor neuron cell death in ALS by repeatedly activating postsynaptic glutamate receptors (Ilieva, Polymenidou, & Cleveland, 2009; Lee, et al, 2016). Under normal conditions, glutamate released into the synapse can be taken up by astrocytes via excitatory amino acid transporters (EAATs).…”

Section: Glutamate and Neuroinflammationmentioning

confidence: 99%

“…ALS is a non-cell autonomous disease, affecting non-neuronal cells such as astrocytes and microglia (Lee, et al, 2016). Astrocyte dysfunction can disrupt their ability to support neurons, leading to motor and non-motor neuron cell death (Philips & Rothstein, 2014).…”

Section: Glutamate and Neuroinflammationmentioning

confidence: 99%

TDP-43 in the spectrum of MND-FTLD pathologies

Heyburn

Moussa

2017

Molecular and Cellular Neuroscience

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The relationship between RNA-binding proteins, particularly TAR DNA binding protein 43 (TDP-43), and neurodegeneration is an important area of research. TDP-43 is involved in so many cellular processes that perturbation of protein homeostasis can lead to countless downstream effects. Understanding what leads to this disease-related protein imbalance and the resulting cellular and molecular effects will help to develop targets for disease intervention, whether it be prevention of protein accumulation, or addressing a secondary effect of protein accumulation. Here we review the current literature of TDP-43 and TDP-43 pathologies, the effects of TDP-43 overexpression and disruption of synaptic proteins through its binding of messenger RNA, leading to synaptic dysfunction. This review highlights some of the still-limited knowledge of the protein TDP-43 and how it can contribute to disease.

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“…Thus, astrocytes regulate glutamate homeostasis by two major CNS glutamate transporters, GLT-1/ EAAT2 and GLAST/EAAT1, which are expressed almost exclusively by astrocytes in adult mammals. In addition, astrocyte dysfunction may be the reason for the observed decrease in neurotrophic factors [12,13], as well as for the oxidative stress [14] and neuroinflammation [15].…”

Section: Introductionmentioning

confidence: 99%

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

Izrael¹,

Guy²,

Itskovitz‐Eldor³

et al. 2018

Astrocyte - Physiology and Pathology

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Astrocytes are the major cell population in the central nervous system (CNS) and play pivotal role in CNS homeostasis and functionality. Malfunction of astrocytes were implicated in multiple neurodegenerative diseases and disorders, including amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), brain stroke, Parkinson's disease (PD), and Alzheimer disease (AD). These new insights led to the rationale that transplantation of healthy and functional human astrocytes could support survival of neurons and be of therapeutic value in treating neurodegenerative diseases. Here, we will mainly focus on the role of astrocytes in ALS disease, the major cell sources for generation of human astrocytes, or astrocyte like cells and show how multiple preclinical studies demonstrate the efficacy of these cells in animal models. In addition, we will cover immerging early stage clinical trials that are currently being conducted using human astrocytes or human astrocyte like cell population.

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Astrocytes and Microglia as Non-cell Autonomous Players in the Pathogenesis of ALS

Cited by 124 publications

References 59 publications

Spinal motor neurons and motor function in older adults

Spinal motor neurons and motor function in older adults

TDP-43 in the spectrum of MND-FTLD pathologies

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

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