Distribution and cellular localization of high mobility group box protein 1 (HMGB1) in the spinal cord of a transgenic mouse model of ALS

Coco, Daniele Lo; Veglianese, Pietro; Allievi, E.; Bendotti, Caterina

doi:10.1016/j.neulet.2006.10.063

Cited by 50 publications

(35 citation statements)

References 22 publications

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“…HMGB1 was indicated to decrease in neurons and to increase in astrocytes with aging (Enokido et al, 2008). When expression and localization of HMBG1 was evaluated in the lumbar SC of SOD1G93A transgenic mice, although intense reactivity was found, no differences were obtained between controls and the SOD1 mice (Lo Coco et al, 2007). However, since HMBG1 was identified in the cytoplasm of astrocytes and microglia in SC samples from ALS patients (Casula et al, 2011) it may trigger TLR signaling pathways.…”

Section: Neurodegenerative Networking In Alsmentioning

confidence: 97%

“…The finding was observed at the late ALS phase and, thus, it will be important to follow the TLR/RAGE cascade in animal models at different stages of the disease. In contrast, a progressive reduction of HMGB1 immunopositive MNs was found at advanced stages and may reflect the loss of MNs, reduced synthesis or enhanced released of the cytokine (Lo Coco et al, 2007). Additional studies are needed to investigate the causative hypothesis indicated for the decreased HMGB1 immunoreactivity in MNs, inasmuch since it can also have beneficial effects on neuroregeneration (Fang et al, 2012).…”

Section: Neurodegenerative Networking In Alsmentioning

confidence: 99%

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Microglia centered pathogenesis in ALS: insights in cell interconnectivity

Brites

Vaz

2014

Front. Cell. Neurosci.

176

137

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Amyotrophic lateral sclerosis (ALS) is the most common and most aggressive form of adult motor neuron (MN) degeneration. The cause of the disease is still unknown, but some protein mutations have been linked to the pathological process. Loss of upper and lower MNs results in progressive muscle paralysis and ultimately death due to respiratory failure. Although initially thought to derive from the selective loss of MNs, the pathogenic concept of non-cell-autonomous disease has come to the forefront for the contribution of glial cells in ALS, in particular microglia. Recent studies suggest that microglia may have a protective effect on MN in an early stage. Conversely, activated microglia contribute and enhance MN death by secreting neurotoxic factors, and impaired microglial function at the end-stage may instead accelerate disease progression. However, the nature of microglial–neuronal interactions that lead to MN degeneration remains elusive. We review the contribution of the neurodegenerative network in ALS pathology, with a special focus on each glial cell type from data obtained in the transgenic SOD1G93A rodents, the most widely used model. We further discuss the diverse roles of neuroinflammation and microglia phenotypes in the modulation of ALS pathology. We provide information on the processes associated with dysfunctional cell–cell communication and summarize findings on pathological cross-talk between neurons and astroglia, and neurons and microglia, as well as on the spread of pathogenic factors. We also highlight the relevance of neurovascular disruption and exosome trafficking to ALS pathology. The harmful and beneficial influences of NG2 cells, oligodendrocytes and Schwann cells will be discussed as well. Insights into the complex intercellular perturbations underlying ALS, including target identification, will enhance our efforts to develop effective therapeutic approaches for preventing or reversing symptomatic progression of this devastating disease.

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Section: Neurodegenerative Networking In Alsmentioning

confidence: 97%

Section: Neurodegenerative Networking In Alsmentioning

confidence: 99%

Microglia centered pathogenesis in ALS: insights in cell interconnectivity

Brites

Vaz

2014

Front. Cell. Neurosci.

176

137

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“…SOD3 (EC-SOD) exists as a copper and zinc-containing tetramer and is located in extracellular spaces. Dysfunction of SOD1 and SOD2 is involved in the regulation of HMGB1 release in cell death (Kang et al, 2011b; Lo Coco et al, 2007; Tang et al, 2011d; Vezzoli et al, 2011; Yao and Brownlee, 2010). In addition, other antioxidant enzymes such as glutathione reductase (Chiang and Maric, 2011; Hoppe et al, 2006), thioredoxin (Vezzoli et al, 2011; Xiang et al, 2011; Xu et al, 2013a), and peroxiredoxins (Shichita et al, 2012) can regulate HMGB1 release.…”

Section: Hmgb1 Releasementioning

confidence: 99%

“…HMGB1 and its receptors such as TLR2, TLR4, and RAGE are increased in reactive glia, whereas they are decreased in degenerating motor neurons in patients with amyotrophic lateral sclerosis, suggesting a possible role in the progression of inflammation and motor neuron degeneration (Casula et al, 2011; Lo Coco et al, 2007). In addition, serum HMGB1 autoantibody is increased in patients with amyotrophic lateral sclerosis compared with patients with Alzheimer's disease and Parkinson's disease (Hwang et al, 2013).…”

Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

803

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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“…Furthermore, this increase of RAGE and its ligands was recapitulated in one of the most commonly employed ALS rodent models, murine lines containing the familial G93A mutation in superoxide dismutase 1 (SOD1), as discovered in human ALS populations [3,99,100]. In these models, nerve growth factor (NGF) is post-translationally modified by oxidation and contributes to RAGE signaling-induced motor neuron death when normal motor neurons are co-cultured with SOD1 G93A astrocytes [101].…”

Section: Amyotrophic Lateral Sclerosis Another Inflammatory Syndromementioning

confidence: 97%