ID 111516
著者
キーワード
prion
prion protein
prion protein-like protein
knockout mice
neurodegeneration
資料タイプ
学術雑誌論文
抄録
Conformational conversion of the normal cellular isoform of prion protein, PrPC, a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety, into the abnormally folded, amyloidogenic prion protein, PrPSc, plays a pivotal role in the pathogenesis of prion diseases. It has been suggested that PrPC might be functionally disturbed by constitutive conversion to PrPSc due to either the resulting depletion of PrPC or the dominant negative effects of PrPSc on PrPC or both. Consistent with this, we and others showed that mice devoid of PrPC (PrP-/-) spontaneously developed abnormal phenotypes very similar to the neurological abnormalities of prion diseases, supporting the concept that functional loss of PrPC might at least be partly involved in the pathogenesis of the diseases. However, no neuronal cell death could be detected in PrP-/- mice, indicating that the functional loss of PrPC alone might not be enough to induce neuronal cell death, one of major pathological hallmarks of prion diseases. Interestingly, it was recently shown that the first identified PrP-like protein, termed PrPLP/Doppel (Dpl), is neurotoxic in the absence of PrPC, causing Purkinje cell degeneration in the cerebellum of mice. Although it is not understood if PrPSc could have a neurotoxic potential similar to PrPLP/ Dpl, it is very interesting to speculate that accumulation of PrPSc and the functional disturbance of PrPC, both of which are caused by constitutive conversion, might be required for the neurodegeneration in prion diseases.
掲載誌名
The Journal of Medical Investigation
ISSN
13496867
13431420
cat書誌ID
AA11166929
AA12022913
出版者
Faculty of Medicine Tokushima University
54
3-4
開始ページ
211
終了ページ
223
並び順
211
発行日
2007-08
EDB ID
171919
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所