TY - JOUR
T1 - Niemann-Pick disease type C yields possible clue for why cerebellar neurons do not form neurofibrillary tangles
AU - Bu, Bitao
AU - Klunemann, Hans
AU - Suzuki, Kinuko
AU - Li, Jin
AU - Bird, Thomas
AU - Jin, Lee-Way
AU - Vincent, Inez
PY - 2002
Y1 - 2002
N2 - It is unknown why cerebellar neurons resist neurofibrillary tangle (NFT) formation. In Niemann-Pick disease Type C (NPC), NFT-mediated neurodegeneration occurs throughout brain, but the cerebellum degenerates conspicuously without NFT. To understand why, we have studied markers of NFT pathogenesis in cerebellum from 17 NPC cases, all having abundant NFT in forebrain. Remarkably, we found that NPC cerebella display several early markers of NFT formation, i.e., hyperphosphorylated tau and an array of cell cycle regulators, suggesting that cerebellar neurons in NPC undergo similar modifications as other neurons that develop NFT. However, cerebellar neurons are deficient in tau, the building block of NFT, and this may be one reason for their inability to form NFT. Even without NFT, cerebellar neurodegeneration may be triggered by the inappropriate activation of the cell cycle cdc2 kinase, and the npc-1 murine model provides an opportunity to test this hypothesis.
AB - It is unknown why cerebellar neurons resist neurofibrillary tangle (NFT) formation. In Niemann-Pick disease Type C (NPC), NFT-mediated neurodegeneration occurs throughout brain, but the cerebellum degenerates conspicuously without NFT. To understand why, we have studied markers of NFT pathogenesis in cerebellum from 17 NPC cases, all having abundant NFT in forebrain. Remarkably, we found that NPC cerebella display several early markers of NFT formation, i.e., hyperphosphorylated tau and an array of cell cycle regulators, suggesting that cerebellar neurons in NPC undergo similar modifications as other neurons that develop NFT. However, cerebellar neurons are deficient in tau, the building block of NFT, and this may be one reason for their inability to form NFT. Even without NFT, cerebellar neurodegeneration may be triggered by the inappropriate activation of the cell cycle cdc2 kinase, and the npc-1 murine model provides an opportunity to test this hypothesis.
KW - Alzheimer's disease
KW - Cell cycle, cdc2
KW - Cerebellum
KW - Hyperphosphorylated tau
KW - Neurodegeneration
KW - Neurofibrillary tangle
KW - Niemann-Pick disease type C
KW - Purkinje neurons
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U2 - 10.1006/nbdi.2002.0551
DO - 10.1006/nbdi.2002.0551
M3 - Article
C2 - 12505421
AN - SCOPUS:0036968946
VL - 11
SP - 285
EP - 297
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 2
ER -