Curcumin protects axons from degeneration in the setting of local neuroinflammation

Million Adane Tegenge, Labchan Rajbhandari, Shiva Shrestha, Aditya Mithal, Suneil Hosmane, Arun Venkatesan

Research output: Contribution to journalArticlepeer-review

Abstract

Axon degeneration is a hallmark of several central nervous system (CNS) disorders, including multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Previous neuroprotective approaches have mainly focused on reversal or prevention of neuronal cell body degeneration or death. However, experimental evidence suggests that mechanisms of axon degeneration may differ from cell death mechanisms, and that therapeutic agents that protect cell bodies may not protect axons. Moreover, axon degeneration underlies neurologic disability and may, in some cases, represent an important initial step that leads to neuronal death. Here, we develop a novel quantitative microfluidic-based methodology to assess mechanisms of axon degeneration caused by local neuroinflammation. We find that LPS-stimulated microglia release soluble factors that, when applied locally to axons, result in axon degeneration. This local axon degeneration is mediated by microglial MyD88/p38 MAPK signaling and concomitant production of nitric oxide (NO). Intra-axonal mechanisms of degeneration involve JNK phosphorylation. Curcumin, a compound with both anti-oxidant and JNK inhibitory properties, specifically protects axons, but not neuronal cell bodies, from NO-mediated degeneration. Overall, our platform provides mechanistic insights into local axon degeneration, identifies curcumin as a novel axon protectant in the setting of neuroinflammation, and allows for ready screening of axon protective drugs.

Original languageEnglish (US)
Pages (from-to)102-110
Number of pages9
JournalExperimental Neurology
Volume253
DOIs
StatePublished - Mar 1 2014

Keywords

  • Axon degeneration
  • Axon protection
  • FAD
  • Focal axonal degeneration
  • JNK
  • Microfluidics
  • Microglia
  • Multiple sclerosis
  • Neuroprotection
  • Nitric oxide

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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