Exosomes of BV-2 cells induced by alpha-synuclein: Important mediator of neurodegeneration in PD

Chang, Chongwang; Lang, Hongjuan; Geng, Ning; Wang, Jing; Li, Nan; Wang, Xuelian

doi:10.1016/j.neulet.2013.06.009

Cited by 135 publications

(114 citation statements)

References 29 publications

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“…However, microglia also release exosomes (Potolicchio et al, 2005; Hooper et al, 2012), which generate IL-1β to the extracellular environment propagating inflammation (Turola et al, 2012). Increased exosome discharge by microglia was observed after stimulation with α-synuclein and such activated exosomes revealed an increased membrane content in TNF-α (Chang et al, 2013). Interestingly, it was shown that mouse MN-like NSC-34 cells overexpressing hSOD1G93A secrete SOD1 via exosomes probably accounting to cell–cell-mediated mutant toxicity in ALS pathogenesis (Gomes et al, 2007).…”

Section: Inflammatory Components In Als and Pathological Cell–cell Comentioning

confidence: 99%

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: Inflammatory Components In Als and Pathological Cell–cell Comentioning

confidence: 99%

Microglia centered pathogenesis in ALS: insights in cell interconnectivity

Brites

Vaz

2014

Front. Cell. Neurosci.

176

137

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“…On the one hand, MVs released by reactive microglia carry pro-inflammatory cytokines [221] and induce an inflammatory reaction in target cells [222]. Microglia-derived MVs also promote precipitation of misfolded proteins in Parkinson's and Alzheimer's disease models [223,224]. On the other hand, microglia stimulated with interferon-γ release exosomes that confer protection on surrounding cells [225].…”

Section: Microglia May Drive Als Pathophysiologymentioning

confidence: 99%

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Rodrı́guez¹,

Mahy²

2016

CMC

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“…We recently demonstrated that ganglioside-containing exosomes, as well as vesicles prepared from extracted exosome lipids and ganglioside-containing model mixtures have the effect to accelerate α-syn aggregation [21]. Secretion of α-syn via exosomes has been proposed to amplify and propagate PD pathology [[37], [38], [39]], and several studies have identified α-syn associated with exosomes [[40], [41], [42]]. We here address a question raised in these previous studies: are the effects observed for ganglioside-containing membranes related to specific interactions between the protein and the ganglioside headgroup, or is it attributed to more generic properties of the lipid, such as, headgroup charge and size, or lipid self-assembly?…”

Section: Introductionmentioning

confidence: 99%

Ganglioside lipids accelerate α-synuclein amyloid formation

Gaspar

Pallbo

Weininger

et al. 2018

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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The deposition of α-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of α-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of α-synuclein monomers and catalyse their aggregation at mildly acidic conditions. Although the extent of this catalytic effect was slightly higher for gangliosides, the results imply that charge interactions are more important than headgroup chemistry in triggering aggregation. In support of this idea, uncharged lipids with large headgroups were not found to induce any conformational change and only weakly catalyse aggregation. Intriguingly, aggregation was also triggered by free ganglioside headgroups, while these caused no conformational change of α-synuclein monomers. Our data reveal that partially folded α-synuclein helical intermediates are not required species in triggering of α-synuclein aggregation.

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Exosomes of BV-2 cells induced by alpha-synuclein: Important mediator of neurodegeneration in PD

Cited by 135 publications

References 29 publications

Microglia centered pathogenesis in ALS: insights in cell interconnectivity

Microglia centered pathogenesis in ALS: insights in cell interconnectivity

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Ganglioside lipids accelerate α-synuclein amyloid formation

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