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
2
Embed
DJ-1 - Abcam€¦ · Our Neurodegeneration antibodies are the best! See our datasheets for customer reviews, enquiries and imagesat Synuclein antibody [4B12 ...
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
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.
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
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