Integrins protect nociceptive neurons in models of paclitaxel-mediated peripheral sensory neuropathy

Gj, Shin; Me, Pero; La, Hammond; Burgos, Anita; Se, Galindo; Bartolini, Francesca; Grueber, Wesley B.

doi:10.1101/829655

Cited by 1 publication

(1 citation statement)

References 79 publications

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“…Of note, the substrate in microfluidic cultures consists of laminin, rather than the Matrigel used in Campenot cultures. A previous study suggests that changes in substrate may alter the timing and dose responses of paclitaxel induced axon degeneration (Shin et al, 2021). We used a higher dose of paclitaxel which is required in non-compartmental cultures (600nM) and also causes axon retraction in microfluidic chambers (FigueS2A-B).…”

Section: Paclitaxel Leads To Sarm1-dependent Axonal Calcium Fluxmentioning

confidence: 99%

Activation of Sarm1 produces cADPR to increase intra-axonal calcium and promote axon degeneration in CIPN

Avizonis

et al. 2021

Preprint

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Cancer patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN), a painful and long-lasting disorder with profound somatosensory deficits. There are no effective therapies to prevent or treat this disorder. Pathologically, CIPN is characterized by a dying-back axonopathy that begins at intra-epidermal nerve terminals of sensory neurons and progresses in a retrograde fashion. Calcium dysregulation constitutes a critical event in CIPN, but it is not known how chemotherapies such as paclitaxel alter intra-axonal calcium and cause degeneration. Here, we demonstrate that paclitaxel triggers Sarm1-dependent cADPR production in distal axons, promoting intra-axonal calcium flux from both intracellular and extracellular calcium stores. Genetic or pharmacologic antagonists of cADPR signaling prevent paclitaxel-induced axon degeneration and allodynia symptoms, without mitigating the anti-neoplastic efficacy of paclitaxel. Our data demonstrate that cADPR is a calcium modulating factor that promotes paclitaxel-induced axon degeneration and suggest that targeting cADPR signaling provides a potential therapeutic approach for treating CIPN.

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Section: Paclitaxel Leads To Sarm1-dependent Axonal Calcium Fluxmentioning

confidence: 99%

Activation of Sarm1 produces cADPR to increase intra-axonal calcium and promote axon degeneration in CIPN

Avizonis

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

Integrins protect nociceptive neurons in models of paclitaxel-mediated peripheral sensory neuropathy

Cited by 1 publication

References 79 publications

Activation of Sarm1 produces cADPR to increase intra-axonal calcium and promote axon degeneration in CIPN

Activation of Sarm1 produces cADPR to increase intra-axonal calcium and promote axon degeneration in CIPN

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