Resveratrol delays Wallerian degeneration in a NAD+ and DBC1 dependent manner

Aldo Calliari, Natalia Bobba, Carlos Escande, Eduardo Nunes Chini

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Axonal degeneration is a central process in the pathogenesis of several neurodegenerative diseases. Understanding the molecular mechanisms that are involved in axonal degeneration is crucial to developing new therapies against diseases involving neuronal damage. Resveratrol is a putative SIRT1 activator that has been shown to delay neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Alzheimer, and Huntington's disease. However, the effect of resveratrol on axonal degeneration is still controversial. Using an in vitro model of Wallerian degeneration based on cultures of explants of the dorsal root ganglia (DRG), we showed that resveratrol produces a delay in axonal degeneration. Furthermore, the effect of resveratrol on Wallerian degeneration was lost when SIRT1 was pharmacologically inhibited. Interestingly, we found that knocking out Deleted in Breast Cancer-1 (DBC1), an endogenous SIRT1 inhibitor, restores the neuroprotective effect of resveratrol. However, resveratrol did not have an additive protective effect in DBC1 knockout-derived DRGs, suggesting that resveratrol and DBC1 are working through the same signaling pathway. We found biochemical evidence suggesting that resveratrol protects against Wallerian degeneration by promoting the dissociation of SIRT1 and DBC1 in cultured ganglia. Finally, we demonstrated that resveratrol can delay degeneration of crushed nerves in vivo. We propose that resveratrol protects against Wallerian degeneration by activating SIRT1 through dissociation from its inhibitor DBC1.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalExperimental Neurology
Volume251
DOIs
StatePublished - Jan 2014

Fingerprint

Wallerian Degeneration
NAD
Breast Neoplasms
Neurodegenerative Diseases
resveratrol
Dissociative Disorders
Nerve Degeneration
Diagnosis-Related Groups
Huntington Disease
Amyotrophic Lateral Sclerosis
Spinal Ganglia
Neuroprotective Agents
Ganglia
Alzheimer Disease

Keywords

  • Axonal degeneration
  • DBC1
  • Resveratrol
  • SIRT1
  • Wallerian degeneration

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Resveratrol delays Wallerian degeneration in a NAD+ and DBC1 dependent manner. / Calliari, Aldo; Bobba, Natalia; Escande, Carlos; Chini, Eduardo Nunes.

In: Experimental Neurology, Vol. 251, 01.2014, p. 91-100.

Research output: Contribution to journalArticle

Calliari, Aldo ; Bobba, Natalia ; Escande, Carlos ; Chini, Eduardo Nunes. / Resveratrol delays Wallerian degeneration in a NAD+ and DBC1 dependent manner. In: Experimental Neurology. 2014 ; Vol. 251. pp. 91-100.
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