TY - JOUR
T1 - The neuroprotective role of attractin in neurodegeneration
AU - Paz, Jeff
AU - Yao, Honghong
AU - Lim, Hyo Sook
AU - Lu, Xin Yun
AU - Zhang, Wei
N1 - Funding Information:
We thank the excellent technical help from Chung Sub Kim. This work is supported partially by the ERC fund from UTHSCSA and by American Heart Association to WZ.
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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.
KW - Attractin
KW - Mitochondria and apoptosis
KW - Neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=34447561758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447561758&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2006.06.014
DO - 10.1016/j.neurobiolaging.2006.06.014
M3 - Article
C2 - 16860906
AN - SCOPUS:34447561758
SN - 0197-4580
VL - 28
SP - 1446
EP - 1456
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 9
ER -