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, 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.
Paz
Jeff
J
Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC6205, San Antonio, TX 78229-3900, USA.
Yao
Honghong
H
Lim
Hyo Sook
HS
Lu
Xin-Yun
XY
Zhang
Wei
W
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000633:toxicity; D000704:Analysis of Variance; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000502:physiology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D009498:Neurotoxins / Q000633:toxicity; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051033:Apoptosis Inducing Factor; C117928:Atrn protein, mouse; D008565:Membrane Proteins; D009498:Neurotoxins; D034741:RNA, Small Interfering; C067713:lactacystin; D045304:Cytochromes c; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D000111:Acetylcysteine