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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

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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.

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Suzuki A, Yamasaki T, Horiuchi M. Absence of

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J Virol 87:13433-13445, 2013.

8) Abe Y, Hashimoto K, Watanabe M, Ohara S,

Sato M, Kawasaki Y, Hashimoto Y, Hosoya M.

Characteristics of viruses derived from nude mice

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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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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

human prion diseases now possible using real-time

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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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Shimizu Y, Kasai K, Matsuura Y, Yokoyama T. The

N-terminal sequence of prion protein consists an

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─ 16 ─