Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy

Melli, Giorgia; Keswani, Sanjay C.; Fischer, Angela; Chen, Weiran; Höke, Ahmet

doi:10.1093/brain/awl058

Cited by 128 publications

(128 citation statements)

References 42 publications

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“…Recent studies indicate that gp120 may induce both neuronal apoptosis and axonal degeneration in cultured rat DRG sensory neurons (Melli G et al, 2006). Binding of gp120 to CXCR4 on sensory axons may directly cause the local axonal degeneration.…”

Section: Neurotoxicity/neuroprotectionmentioning

confidence: 99%

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

Ransohoff

2008

Progress in Neurobiology

307

245

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Chemotactic cytokines (chemokines) have been traditionally defined as small (10-14 kDa) secreted leukocyte chemoattractants. However, chemokines and their cognate receptors are constitutively expressed in the central nervous system (CNS) where immune activities are under stringent control. Why and how the CNS uses the chemokine system to carry out its complex physiological functions has intrigued neurobiologists. Here, we focus on chemokine CXCL12 and its receptor CXCR4 that have been widely characterized in peripheral tissues and delineate their main functions in the CNS. Extensive evidence supports CXCL12 as a key regulator for early development of the CNS. CXCR4 signaling is required for the migration of neuronal precursors, axon guidance/pathfinding and maintenance of neural progenitor cells (NPCs). In the mature CNS, CXCL12 modulates neurotransmission, neurotoxicity and neuroglial interactions. Thus, chemokines represent an inherent system that helps establish and maintain CNS homeostasis. In addition, growing evidence implicates altered expression of CXCL12 and CXCR4 in the pathogenesis of CNS disorders such as HIVassociated encephalopathy, brain tumor, stroke and multiple sclerosis (MS), making them the plausible targets for future pharmacological intervention.

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Section: Neurotoxicity/neuroprotectionmentioning

confidence: 99%

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

Ransohoff

2008

Progress in Neurobiology

307

245

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“…Mixed DRG cultures were plated as above for 24 h. These DRG cultures were continuously treated with AraC (10 Ϫ6 M for 1 week), as described (Melli et al, 2006), and examined immunocytochemically with anti-S100 and anti-␤-IIItubulin Abs to assess the presence of Schwann cells. Our results showed that, after AraC treatment, Ͻ5% of cells stained for S100 in DRG cultures (Fig.…”

Section: Antibodies Inhibit Neurite Outgrowth Of Embryonic and Postnamentioning

confidence: 99%

Anti-Ganglioside Antibody-Mediated Activation of RhoA Induces Inhibition of Neurite Outgrowth

Zhang¹,

Lehmann

Manoharan

et al. 2011

J. Neurosci.

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Anti-ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barré syndrome (GBS). Some studies indicate that these Abs, including those with GD1a reactivity, are associated with poor prognosis and/or incomplete recovery. We recently demonstrated that a disease-relevant anti-ganglioside Ab with GD1a reactivity inhibits axon regeneration after PNS injury in an animal model (Lehmann et al., 2007). An implication of these findings is that anti-GD1a Abs can mediate inhibition of axon regeneration and limit recovery in some patients with GBS. The downstream inhibitory intracellular signaling that mediates anti-ganglioside Ab-induced axon inhibition remains unclear. In the current study, we show that disease-relevant and GBS patient's anti-ganglioside Abs can inhibit neurite outgrowth in dissociated primary neuronal cultures. Activation of small GTPase RhoA and its key downstream effector Rho kinase (ROCK) are critical mediators of growth cone and neurite outgrowth inhibition. Therefore, we examined the role of these intracellular signaling molecules in our primary neuronal cultures by molecular and pharmacologic approaches. Our results show that the Ab-mediated inhibition of neurite outgrowth involves the activation of RhoA and ROCK pathway and this activation is through the engagement of specific cell-surface gangliosides by Abs. In summary, these studies directly link patient autoantibodies to an intracellular inhibitory signaling pathway involved in anti-ganglioside Abmediated inhibition of neurite outgrowth.

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“…In adult animals SDF-1 assumes yet another role, acting as a neurotransmitter that can stimulate DRG neuron excitability and produce pain (Bhangoo et al, 2007;Oh et al, 2001). Furthermore, the expression of CXCR4 receptors by DRG neurons or glia may act as a binding site where T-tropic strains of HIV-1 can produce neuronal excitation and pain or possibly neuronal death (Melli et al, 2006;Oh et al, 2001). Therefore, it is clear that CXCR4 signaling has an important role during the entire lifetime of a DRG neuron.…”

Section: Development Of the Nervous Systemmentioning

confidence: 99%

CXCR4 signaling in the regulation of stem cell migration and development

Miller¹,

Banisadr²,

Bhattacharyya³

2008

Journal of Neuroimmunology

160

125

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The regulated migration of stem cells is a feature of the development of all tissues and also of a number of pathologies. In the former situation the migration of stem cells over large distances is required for the correct formation of the embryo. In addition, stem cells are deposited in niche like regions in adult tissues where they can be called upon for tissue regeneration and repair. The migration of cancer stem cells is a feature of the metastatic nature of this disease. In this article we discuss observations that have demonstrated the important role of chemokine signaling in the regulation of stem cell migration in both normal and pathological situations. It has been demonstrated that the chemokine receptor CXCR4 is expressed in numerous types of embryonic and adult stem cells and the chemokine SDF-1/CXCL12 has chemoattractant effects on these cells. Animals in which SDF-1/CXCR4 signaling has been interrupted exhibit numerous phenotypes that can be explained as resulting from inhibition of SDF-1 mediated chemoattraction of stem cells. Hence, CXCR4 signaling is a key element in understanding the functions of stem cells in normal development and in diverse pathological situations.

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Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy

Cited by 128 publications

References 42 publications

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

Anti-Ganglioside Antibody-Mediated Activation of RhoA Induces Inhibition of Neurite Outgrowth

CXCR4 signaling in the regulation of stem cell migration and development

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