Caffeic acid phenethyl ester extends survival of a mouse model of amyotrophic lateral sclerosis

C. V. Fontanilla, X. Wei, L. Zhao, B. Johnstone, Robert Pascuzzi, Martin Farlow, Yansheng Du

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

There is currently very limited effective pharmacological treatment for amyotrophic lateral sclerosis. Recent evidence suggests that caffeic acid phenethyl ester has strong anti-inflammatory, anti-oxidative, and anti-neuronal death properties; thus, the present study tested the effects of caffeic acid phenethyl ester in mice expressing a mutant superoxide dismutase (SOD1G93A) linked to human amyotrophic lateral sclerosis. Administration of caffeic acid phenethyl ester after symptom onset significantly increased the post-onset survival and lifespan of SOD1G93A mice. Moreover, immunohistochemical analysis detected less activation of microglia and astrocytes and higher motor neuron counts at an early symptomatic stage (7 days following onset) in the spinal cords of SOD1G93A mice given caffeic acid phenethyl ester treatment. Additionally, lower levels of phosphorylated p38, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death, were observed in the spinal cords of SOD1G93A mice treated with caffeic acid phenethyl ester for 7 days. These results indicate that caffeic acid phenethyl ester may represent a novel and effective therapeutic for the treatment of amyotrophic lateral sclerosis, and these significant neuroprotective effects observed in a commonly used amyotrophic lateral sclerosis mouse model validate the therapeutic potential of caffeic acid phenethyl ester for slowing disease progression by attenuating the neuroinflammation and motor neuron cell death associated with clinical amyotrophic lateral sclerosis pathology.

Original languageEnglish
Pages (from-to)185-193
Number of pages9
JournalNeuroscience
Volume205
DOIs
StatePublished - Mar 15 2012

Fingerprint

Amyotrophic Lateral Sclerosis
Motor Neurons
Spinal Cord
Microglia
Neuroprotective Agents
p38 Mitogen-Activated Protein Kinases
caffeic acid phenethyl ester
Astrocytes
Superoxide Dismutase
Disease Progression
Cell Death
Anti-Inflammatory Agents
Pharmacology
Pathology
Inflammation
Survival
Therapeutics

Keywords

  • ALS
  • Caffeic acid phenethyl ester
  • Neurodegeneration
  • Neuroprotection
  • SOD1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Caffeic acid phenethyl ester extends survival of a mouse model of amyotrophic lateral sclerosis. / Fontanilla, C. V.; Wei, X.; Zhao, L.; Johnstone, B.; Pascuzzi, Robert; Farlow, Martin; Du, Yansheng.

In: Neuroscience, Vol. 205, 15.03.2012, p. 185-193.

Research output: Contribution to journalArticle

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