The neuroprotective role of attractin in neurodegeneration

Loss-of-function mutations of attractin (Atrn) in animals result in age-dependent progressive neurodegeneration including neuronal cell death, hypomyclination 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 Atm 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 Atm for neurodegenerative diseases. (C) 2006 Elsevier Inc. All rights reserved.