title: Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease.
abstract: PrPSc is formed from a normal glycosylphosphatidylinositol (GPI)-anchored prion protein (PrPC) by a posttranslational modification. Most GPI-anchored proteins have been shown to be cleaved by GPI phospholipases. Recently, GPI-phospholipase D (GPI-PLD) was shown to be a strictly specific enzyme for GPI anchors. To investigate the involvement of GPI-PLD in the processes of neurodegeneration in prion diseases, we examined the mRNA and protein expression levels of GPI-PLD in the brains of a prion animal model (scrapie), and in both the brains and cerebrospinal fluids (CSF) of sporadic and familial Creutzfeldt-Jakob disease (CJD) patients. We found that compared with controls, the expression of GPI-PLD was dramatically down-regulated in the brains of scrapie-infected mice, especially in the caveolin-enriched membrane fractions. Interestingly, the observed decrease in GPI-PLD expression levels began at the same time that PrPSc began to accumulate in the infected brains and this decrease was also observed in both the brain and CSF of CJD patients; however, no differences in expression were observed in either the brains or CSF specimens from Alzheimer's disease patients. Taken together, these results suggest that the down-regulation of GPI-PLD protein may be involved in prion propagation in the brains of prion diseases.
authors: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Korea.
authors: Jae-Kwang
authors: JK
authors: Jin
authors: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Korea.
authors: Byungki
authors: B
authors: Jang
authors: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Korea.
authors: Hyoung Tae
authors: HT
authors: Jin
authors: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Korea.
authors: Eun-Kyoung
authors: EK
authors: Choi
authors: Department of Neurophysiology and Brain Science, Nagoya City University Graduate, School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors: Cha-Gyun
authors: CG
authors: Jung
authors: Choju Medical Institute, Fukushimura Hospital, Toyohashi 441-8124, Japan.
authors: Hiroyasu
authors: H
authors: Akatsu
authors: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Korea.
authors: Jae-Il
authors: JI
authors: Kim
authors: Department of Virology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, United States of America.
authors: Richard I
authors: RI
authors: Carp
authors: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Korea.
authors: Yong-Sun
authors: YS
authors: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000473:pathology*; D010739:Phospholipase D / Q000134:cerebrospinal fluid / Q000378:metabolism*; D017096:Prion Diseases / Q000201:enzymology / Q000473:pathology*
chemical_list: D010739:Phospholipase D; C065017:glycoprotein phospholipase D