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SSPE PML
1 2162Creutzfeldt-Jakob CJD
PrPSc RT-QuICMRI
MlpBvPrP
PPSJACOP
2 SSPE 2012 88
SSPE FT-CONH2
3 PML JC JCV 7 99PML JCV agnoprotein
AP3D JCV oligodendroglioma TNF- JCV4 3
2014 26 3http://prion.umin.jp/
─ 1 ─
MRI
SSPEPML
3
Creutzfeldt-JakobvCJD CJD dCJD
18
2005 vCJD
Yamada et al. Lancet 2006 dCJD2/3
Nozaki, Yamada et al. Brain 2010 198020
SSPE
SSPESSPE
SSPE
MV
─ 2 ─
PML HIV
PMLJC JCV
3
2
CJD
EuroCJDSSPE
1)
1999 4 CJD
dCJD
JannettadCJD
MRICJD
Gerstmann-Sträussler-Scheinker GSSP102L-129M PET
PET
A
MRI DWI
CSF109
14-3-3 PrPSc
RT-QuIC CSF
H-FABP
H-FABPCSF protein misfolding cyclic
amplification PMCA PrP
PrPC CJDPMCA
Neuro2a N2a PrPC
PrPSc
ICR RML22L
PrPC DNA
PrPHpL PrP DNA
checkpoint kinase 1 chk1
bank vole Myodes glareolus PrP BvPrP
─ 3 ─
TgBv
KiBv
BSE
BSE C-BSE
BSE H-BSE L-BSE
PPS
GSS
PrP
NMR FT-IR CD
PrPSc
cell ELISA
2) SSPE
SSPE
SSPE 2007
5 SSPE
microtubule-associated protein
2 MAP2
SSPE
14 CSF 15 13 CSF
13 ELISA
Nectin-4/PVRL4 SSPE
SSPE
SSPE
MV F
SSPE
MV H
F
SSPE
SSPE-Kobe-1
M F H
MV
SSPE
1
1,2,4 triazole-3-carboxamide T-CONH2 MV
3) PML
PML
PML CSF JCV
DNA PCR
PCR
JCV PML
2010 6 2013 6
JCV-PCR
38 PML
PML
2012 11 2013 10
PML
PML PML
JCV
─ 4 ─
- viroporinJCV
agnoproteinyeast 2-hybrid system
agnoprotein
oligodendroglioma astrocytomaJCV
HIV-PML HIVTNF- JCV
IMR-32TNF- JCV
4)
3
1)
2012 9 4281 2162922 1240
150-200CJD 1655 77%
CJD genetic CJD 325 15% dCJD 84 5%vCJD 1 0.05% GSS 85 4% FFI 4
0.2% 441 dCJD
25 3147
dCJD 2623 88%
Lyodura®
50 61 11 199914 11 2
1
vertigo 0% vs 28%; P=0.083 0% vs 28%; P=0.083
91% 100% 64% 45%
73% 50% 73%
64% vs 90%; P=0.098 MRI
CJD PrP 129MM 1 PrP 2 PrP
2 PrP2 PrP
1 PrP MRI
GSS P102L-129M PET11C-PIB PET 11C-BF-227
PrP 3F4
dCJD 16 35-8116 13
A 16 503
35 39 41 AA
MRI DWI
─ 5 ─
CSF 109
14-3-3 RT-QuIC
88.9% 85.3% 78.9%
MM2- RT-QuIC
14-3-3
RT-QuIC 72.5%
6.4
4
H-FABP CJD 9
H-FABP
DLB/PDD 8
H-FABP
PMCA
MM1 PMCA
MV2 VV2 dCJD
Hu129V
PrPSc E219Q M232R
vCJD
Neuro2a
PrP
PrPC 132
135 4 14 3 3
14-3-3 PrPC
Tom20 Tom22 Tom 70
Tom70 PrPC
PrP
Mlp
Mlp PrP
mlp1mlp2
PrP
PrPSc
PrPSc
PrPSc
PrPC
GluR3
NR1
DNA
chk1
HpL-EM chk1
18
24
DNA
PrPC DNA
TgBv KiBv CJD
TgBv
KiBv
KiBv
CJD BSE BSE H L
C-BSE
L-BSE
C-BSE L-BSE
PrP
PrP C- L-BSE
─ 6 ─
PPS11 CJD 6 dCJD
2 CJD/GSS3 2013V180I CJD 10
1 38 4 774
3
6 1
CJD4 /
Japanese Consortium of Prion Disease: JACOP
GSSGSS 20
30
NMRPrP pH 2.9 fibrils pH 7.5-like fibrils
pH 7.5-like fibrils pH 7.5 fibrils
Tga20
pre-T cell receptor alpha
PrPSc cell ELISA96
WST
PrPmAb132 ELISA PrPSc
1 log
252
13
2 10CJD
2) SSPE SSPE
891/147060.6% 88 2007
1533/64 51.5%
40 2020 1972 2008
13 49 26.91510 2 2 6 22 4
15 5 1
Jabbour
31 19 115
15 4
─ 7 ─
Jabbour 19 1585% 32 80%
2000 2012 84 1041990
2012 111
6 1
30 SSPE
MAP2 CSF MAP2 SSPE
p<0.01 MAP2
Nectin-4/PVRL4 SSPEallele genotypehaplotype
SSPE
295
18 33
15 12 76 5 5
5 SSPE
SSPE FSSPE
MV FT461I S103I/N462S/N465S F
F
MV MV
SSPE-Kobe-1
M F HSSPE-Kobe-1 MV
F /
F H
F HM /
SSPE SSPE-Kobe-1
T-CONH2 MV EdEC50 7.1 g/mL 10.3
g/mLHPLC T-CONH2
T-CONH2
T-CONH2
T-CONH2
3) PML
PML JCVPCR
19 25 12 1,04023 25 536 99
23 25 51 PML19 22 4
3 23 425 12
PML 194 PML HIV
─ 8 ─
3PML
PML
2010 6 2013 6 38PML
CSF
HIV-PML 26.3%
PML53
1 PMLMS
Natalizumab PMLJCV MRI PML
PML
PMLHIV-PMLHIV-PML2013 PMLAmerican Academy of Neurology AAN
PML PML
10JCV controlled anti-viral inflammation
IRIS
PML-IRIS
JCV PML with controlled anti-viral inflammation
JCV agnoprotein
adaptor protein complex 3AP3D agnoprotein AP3D
viroporinagnoprotein AP3DJCV
Oligodendroglioma astrocytomaJCV
oligodendroglioma U87oligodendroglioma
A172 astrocytomaKMG4 U251
IMR-32 tumor necrosis factor-alpha TNF- JCV
JCV TNF-JCV Large T VP1
real-time RT-PCR Large T
NF- B p65
p65
4)
3
25 122014
http://prion.umin.jp/
26 3
25 7 21-22
SSPE
PML PML 201325 1
2013
─ 9 ─
1)
150-200 BSE vCJD2005
Yamada et al. Lancet 2006 dCJD5
1472/3 1980
302010
CJD2
PrPSc
PrPSc
PrPSc
dCJDvertigo
PrPSc
8 MRI
CJD 1 MM1+2MM2-
MRIMM1
MM2- 1 + 2CJD 1
GSS P102L-129M PET
11C-BF-227 PrP
11C-PIB PET
PET PrP
dCJD A A
A
CJD
Alzheimermisfolding
MRI DWI
DWI
CSF 14-3-3
RT-QuIC 3PrP
RT-QuICRT-QuIC
CSF
H-FABPDLB/PDD
PrPC PMCA
PrPSc 129VPrPC
Cell-PMCA MV2 VV2
dCJD CJD1
vCJD 219 232
CSF
─ 10 ─
PrP
PrPC
PrP 132-135 14-3-3Tom70
Mlp
Mlp nuclear basket
mlp1mlp2
mlp1mlp2PrP
PrPMlp
PrP
PrPSc
PrPSc PrPSc
Uchiyama et al. Nat Commun 2013
PrPC DNA
DNA PrPC
BvPrP CJD
KiBv PrPKiBv CJD BSE
BSE H L
C-
L-BSE PrP
BSEPrPC PrPres cell to cell
C-BSEGT1-7
BSE
CJD BSE
PPS
PPS
JACOP
PrP NMR PrP
─ 11 ─
PrPC
PrPSc cell ELISA1 log
2) SSPE
SSPE2007 5 2012
2007
SSPE
SSPE
SSPE
SSPE
CSF MAP2SSPE CSF SSPE
CSF MAP2
SSPE
Nectin-4/PVRL4
SSPE allelegenotype haplotype
Nectin-4/PVRL4 SSPE
SSPESSPE
SSPE
MV H FMV
─ 12 ─
F SSPE
SSPE F
F HSLAM nectin 4
SSPE-Kobe-1
SSPE-Kobe-1M F
H
SSPE-Kobe-1 RNA RNAMV
F H M/
T-CONH2
MV Vero
T-CONH2
T-CONH2
3) PML
PML JCVPCR 7
PML
PML HIV
CSF
Natalizumab PML
HIV-PML
HIV-PML
AAN PMLPML
2013 AANdefinite
PML
PML PML10% JCV
controlled anti-viral inflammationIRIS
JC agnoprotein viroporin
poreAP3D
Suzuki et al. Proc Natl Acad Sci USA 2013agnoprotein AP3D
JCV
Oligodendroglioma U87JCV
oligodendroglia JCV
Oligodendroglioma A172
oligodendroglia JCV
IMR-32HIV Tat JCV
TNF-JCV
oligodendroglioma TNF-
─ 13 ─
JCVHIV-1
TNF- JCV
4) 2014
25 12 26 3PML 2013
SSPE
20142002 1
1) 2162
CJDA GSS PET
MRI DWICSF
PrPSc RT-QuIC CSFPMCA MV2 VV2
vCJD PrPC
PrPC
Mlp
BvPrP
PPS
JACOP
2) SSPE 2012 88
SSPEF
T-CONH2
3) PML JCV PCR
7 99 PML
JCV agnoproteinAP3D JCV
oligodendroglioma TNF- JCV
4) 3
201426 3
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─ 14 ─
Autophagy 9:1386-1394, 2013.
2) Uchiyama K, Muramatsu N, Yano M, Usui T,
Miyata H, Sakaguchi S. Prions disturb post-Golgi
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3) Suzuki T, Orba Y, Makino Y, Okada Y,
Sunden Y, Hasegawa H, Hall WW, Sawa H.
Viroporin activity of the JC polyomavirus is regulated
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4) Shirogane Y, Watanabe S, Yanagi Y.
Cooperation: another mechanism of viral evolution. Trends Microbiol 21:320-324, 2013.
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Yoshida M, Yuasa T, Izumi Y, Kaji R. Increased
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2013.
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Nozaki I, Hamaguchi T, Nakamura Y, Kitamoto T,
Shirabe S, Murayama S, Yamada M,
Tateishi J, Mizusawa H. Relationships between
clinicopathological features and cerebrospinal fluid
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15) Sano K, Satoh K, Atarashi R, Takashima H,
Iwasaki Y, Yoshida M, Sanjo N, Murai H,
Mizusawa H, Schmitz M, Zerr I, Kim YS, Nishida N.
Early detection of abnormal prion protein in genetic
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16) Kishimoto Y, Hirono M, Atarashi R, Sakaguchi S,
Yoshioka T, Katamine S, Kirino Y. Age-dependent
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protein-deficient mice. PLoS ONE 8:e60627, 2013.
17) Masujin K, Kaku-Ushiki Y, Miwa R, Okada H,
Shimizu Y, Kasai K, Matsuura Y, Yokoyama T. The
N-terminal sequence of prion protein consists an
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─ 16 ─