The neuroprotective role of attractin in neurodegeneration

Jeff Paz, Honghong Yao, Hyo Sook Lim, Xin Yun Lu, Wei Zhang

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Loss-of-function mutations of attractin (Atrn) in animals result in age-dependent progressive neurodegeneration including neuronal cell death, hypomyelination and vacuolation. The mechanisms of how age-dependent neurodegeneration occurs in these animals are not clear. In this study, we found that reducing the endogenous expression level of Atrn exacerbated, whereas overexpressing Atrn protected against, the neuronal cell death caused by the neurotoxins, 1-methyl-4-phenylpyridinium (MPP+) and lactacystin. In addition, both MPP+ and lactacystin-induced cytochrome c and apoptosis inducing factor (AIF) release, which was inhibited by overexpressing Atrn and enhanced by knocking down Atrn, indicating that Atrn may be involved in regulating the mitochondrial function. Furthermore, we found that vast majority of the dopaminergic neurons in mice express Atrn and its expression decreases with age. Our findings demonstrated that Atrn may play a protective role against environmental toxins, and implied a potential therapeutic effect of Atrn for neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)1446-1456
Number of pages11
JournalNeurobiology of Aging
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Keywords

  • Attractin
  • Mitochondria and apoptosis
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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