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www.abcam.com Pathways of Parkinson’s Disease Abcam's range of first class antibodies to Parkinson's Disease-related targets is growing - 70 products so far. www.abcam.com/neuroscience aggregation UPS misfolded protein E1 (Dorfin) (SIAH) O-linked glycosylation Neurodegeneration Protofibrils fibrils mitochondrial DNA polymorphisms ATP Amp+PPi -synuclein substrates Ub Ub Ub Ub Ub Ub Ub Ub Ub Ub Ub Ub Ub degraded protein Ca 2+ p25 Cdk5 CAK p35 c-Abl Cdk5 Ub Ub Ub Ub Ub Ub Ub Ub Ub DJ-1 PINK-1 Death stimuli Calpains Cdk5-p25 SP16 Lewy body Dorfin P Oxidative stress Nuclear targets e.g MEF2 p53 Cytoplasmic targets e.g tau NMDAR Cell survival Dopamine oxidation mitochondrial dysfunction Genetic Mutation Toxicity DA DA DA P PINK-1 S DJ-1 Sp22 tubulins p38 Synphilin-1 cdcrel-1 Cyclin E CHIP Synaptotagmin x PACRG PGP9.5 UBL Ring 1 Ring 2 IBR (Parkin) Ubch8 E2 Ubch7 UCHL1 Mutations in genes such as Parkin, DJ-1, synuclein, UCHL1, and PINK1 lead to disorders that variably resemble Parkinson's disease (PD). Parkin, Dorfin and SIAH are E3 ubiquitin ligases linked to PD (substrates unknown). DJ-1 and PINK1 appear to protect against mitochondrial damage; PINK1 functionally regulates mitochondria via phosphorylation (specific substrates unknown); DJ-1 by conversion to an acidic isoform after oxidative or environmental stress and translocation to the outer mitochondrial membrane. An abnormal increase in synuclein levels leads to the formation of protofibrils and insoluble fibrils, followed by proteasomal impairment, a process that cannot be prevented in the absence of functional Parkin. Oxidative stress, energy crisis (i.e., ATP depletion) and the activation of the programmed cell death machinery are also believed to be factors that trigger the death of dopaminergic neurons in PD. parkinsons disease alphabetical 29/7/05 9:19 Page 1
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Page 1: DJ-1 - Abcam€¦ · Our Neurodegeneration antibodies are the best! See our datasheets for customer reviews, enquiries and imagesat  Synuclein antibody [4B12 ...

www.abcam.comPathways of Parkinson’s Disease

Abcam's range of first classantibodies to Parkinson's Disease-relatedtargets is growing - 70 products so far.www.abcam.com/neuroscience

aggregation

UPSmisfolded

protein

E1

(Dorfin)(SIAH) O-linked

glycosylation

Neurodegeneration

Protofibrilsfibrils

mitochondrialDNA polymorphisms

ATPAmp+PPi

�-synuclein

substrates

Ub Ub Ub Ub Ub Ub Ub UbUb

UbUb

UbUb

degradedprotein

Ca2+

p25

Cdk5

CAK p35c-Abl

Cdk5

UbUb

Ub

Ub

Ub

Ub

Ub

Ub

Ub

DJ-1PINK-1

Death stimuli

CalpainsCdk5-p25

�SP16

Lewy bodyDorfin P

Oxidativestress

Nucleartargets

e.g MEF2 p53

Cytoplasmictargetse.g tau

NMDAR

Cellsurvival

Dopamineoxidation

mitochondrial

dysfunction

Genetic Mutation

Toxicity

DA DA DA

PPINK-1 S

DJ-1

Sp22�

tubulins

p38

Synphilin-1

cdcrel-1Cyclin E

CHIPSynaptotagminx

PACRG

PGP9.5

UBL Ring 1 Ring 2IBR(Parkin)

Ubch8 E2 Ubch7

UCHL1

Mutations in genes such as Parkin, DJ-1, �synuclein, UCHL1, and PINK1 lead to disorders that variably resemble Parkinson's disease (PD). Parkin, Dorfin and SIAH are E3 ubiquitin ligases linked to PD(substrates unknown). DJ-1 and PINK1 appear to protect against mitochondrial damage; PINK1 functionally regulates mitochondria via phosphorylation (specific substrates unknown); DJ-1 byconversion to an acidic isoform after oxidative or environmental stress and translocation to the outer mitochondrial membrane. An abnormal increase in �synuclein levels leads to the formation ofprotofibrils and insoluble fibrils, followed by proteasomal impairment, a process that cannot be prevented in the absence of functional Parkin. Oxidative stress, energy crisis (i.e., ATP depletion) and theactivation of the programmed cell death machinery are also believed to be factors that trigger the death of dopaminergic neurons in PD.

parkinsons disease alphabetical 29/7/05 9:19 Page 1

Page 2: DJ-1 - Abcam€¦ · Our Neurodegeneration antibodies are the best! See our datasheets for customer reviews, enquiries and imagesat  Synuclein antibody [4B12 ...

Our Neurodegeneration antibodies are thebest! See our datasheets for customerreviews, enquiries and images atwww.abcam.com/neuroscience

Synuclein antibody [4B12] (ab1904)

Synuclein is found at presynaptic terminals and in dopaminergicneurons. It can form filamentous aggregates that are the major,non amyloid component of intracellular inclusions in Parkinson's.Synuclein induces fibrillization of tau and reduces neuronalresponsiveness to various apoptotic stimuli, leading to decreasedcaspase 3 activation.

IHC-P using ab1904 (shown here)clearly labels Synuclein-positiveLewy bodies in dystrophic neuritesin the CA2 sector of the hippocampus.

Applications tested for ab1904:� dotblot/western blot � ELISA � immunoprecipitation� immunohistochemistry (formalin-fixed paraffin-embedded sections)� immunohistochemistry (frozen sections) � immunocytochemistry

Spotlight: Top Parkinson’s products

PGP9.5 antibody [13C4 / I3C4] - Neuronal Marker (ab8189)

Protein gene product 9.5 (PGP9.5) hydrolyzes small C-terminaladducts of ubiquitin to generate the ubiquitin monomer. Expression ofPGP9.5 is highly specific to neurons and to cells of the diffuseneuroendocrine system and their tumors. It is present in all neurons.

ab8189 is a robust antibody fordetecting PGP9.5 inimmunohistochemistry, as shown herein free floating rat brain tissue section.

Applications tested for ab8189:� immunofluorescence � immunohistochemistry

(frozen section,paraffin embedded)

www.abcam.com/neuroscience

www.abcam.com

Target Datasheet Clonality Applicationswww.abcam.com/ab tested

UPS substratesc-Abl 15130 P WB, IP, IHC-P

c-Abl [8E9] 3227 M IP, IF, IHC-P

CAK [MO1.1] 9516 M IHC-Fr

Cyclin E 7959 P WB, IP, IHC-P, IHC-Fr

p38 7952 P IHC-Fr, IP, WB

p38 (phospho T180 + Y182) 4822 P WB

p38 [C1.7] 19443 M FACS, Mct

Synphilin-1 6179 P WB, IHC-P, IHC-Fr

Synaptotagmin 10104 P WB, IF

SignallingCalpain 1 15813 P WB, ELISA, IP, IHC

Calpain 1 [9A4H8D3] 3589 M WB, IHC

Calpain 2 16261 P ELISA, IHC-Fr, IP, WB

Calpain 2 [1E8] 713 M ELISA, IF, WB

Calpain 3 10823 P IHC-Fr, IP, WB

Calpain 4 [156] 3514 M WB

Calpain 5 16322 P ELISA, IHC-P, IP, WB

Calpain 6 16257 P WB, ELISA, IHC-Fr, IP

Calpain 7 16356 P ELISA, IHC-P, IP, WB

Calpain 9 22521 P ELISA, IHC, IP, WB

Calpain 10 10820 P IHC-Fr, IP, WB

p31 Cdk5 [DC17 + DC34] 2362 M WB, IP, IHC-P

p35 10570 P WB

NMDAR1 C1 6484 P IHC, IP, WB

NMDAR1 [R1JHL] 1880 M WB

NMDAR1 N1 6483 P IHC, IP, WB

NMDAR2A 108 P AF, IHC-F, IHC-Fr, IP, WB

NMDAR2B 109 P AF, IHC-F, IHC-Fr, IP, WB

NMDAR2B (phospho Y1472) 3856 P WB

NMDAR2C 110 P IHC, IP, WB

Ubiquitin 7780 P WB, IHC-P, IHC-Fr, IF

Ubiquitin [10C2-2] 411 M WB, IHC-P, IHC-Fr, AP

KEY: M- Monoclonal P-Polyclonal

Target Datasheet Clonality Applicationswww.abcam.com/ab tested

Parkin / PARKPARK7 4150 P WB

PARK7 [malphaDJ-1/E2.19] 11251 M ICC, WB

Parkin 6177 P ELISA, IHC-Fr, IHC-P

Synucleinalpha Synuclein 6162 P ICC, IHC-Fr, IHC-P, WB

alpha Synuclein 10789 P Fast track

(phospho Y125)

alpha Synuclein [4D6] 1903 M ELISA, IHC-Fr, IHC-P, WB

alpha Synuclein [4B12] 1904 M ELISA, IHC-Fr, IHC-P, WB

alpha Synuclein [syn204] 3309 M WB

beta Synuclein 6165 P ICC, IHC-Fr, IHC-P, WB

gamma Synuclein 6169 P IHC, IHC-Fr, IHC-P, WB

pan Synuclein 6176 P IHC-Fr, IHC-P, WB

DORFIN 3997 P Fast track

HMGB1 11972 P WB

HMGB1 [HAP46.5] 12029 M ELISA, WB

HMGB1 [4C3] 11354 M WB

HMGB1 [KS1] 13540 M WB

Synphilin 1 6179 P IHC-Fr, IHC-P, WB

VCP [5] 11433 M IHC-Fr, IHC-P, IP, WB

Other Parkinson’s markersALDH1A1 9883 P WB

APH1a 19390 P IF, IP, WB

CCKAR 14441 P WB

Nurr1 12261 P Fast track

PGP9.5 10404 P IF, IHC-Fr, WB

PGP9.5 [10A1] 10358 M IHC-Fr, WB

PGP9.5 [13C4 / I3C4] 8189 M IF, IHC-F, IHC-Fr, IHC-P

Pink-1 23707 P IHC-P, WB

SIAH1 2237 P WB

parkinsons disease alphabetical 29/7/05 9:19 Page 2