Antibodies for Parkinson’s Disease - FocusOn 131

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder of the central nervous system characterized by tremor, muscle rigidity, postural abnormalities and slowed movement (bradykinesia), with dementia manifesting in 20 % of the afflicted. Onset before age 20 is categorized as juvenile-onset, before age 50 as early-onset and after age 50 as late-onset PD. After Alzheimer's disease, PD is the second most common neurodegenerative disorder. Symptoms occur from decreased stimulation of the motor cortex by the basal ganglia, resulting from insuffi-cient formation of dopamine produced in the dopaminergic neurons in the midbrain (especially in the substantia nigra).

Mutations in SNCA, UCHL1, PARK8/LRRK2 and PARK3 result in autosomal dominant PD, while mutations in PARK2, PARK7, and PINK1 result in autosomal recessive PD. NR4A2 and SNCAIP have been identified as susceptibility genes for PD.

Alpha-synuclein (SNCA) is an acidic neuronal protein. Accumulation of insoluble fibrils of aggregated SANCA protein is found in the central pathologic feature of PD, the Lewy bodies. Therefore, PD is generally considered a synucleinopathy.

Fig. 1: Formalin-fixed, paraffin-embedded (FFPE) human brain tissue stained with alpha-synuclein antibody Cat.-No. AP15807PU-N

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme. Expression of UCHL1 is highly specific to neurons and to cells of the diffuse neuroendocrine system and their tumors. A polymorphism in the UCHL1 gene appears to reduce the risk of developing PD, but it is unclear how this variation protects against PD. In contrast, a point mutation in the gene encoding this protein is implicated as the cause of PD in one case. The gene is also associated with Alzheimer's disease and required for normal synaptic and cognitive function.

Leucine-rich repeat kinase 2 (PARK8/LRRK2) is a large, complex protein with multiple enzymatic and protein-interaction domains, each of which are targeted by pathogenic mutations in familial PD.

Fig. 2: Immunofluorescence of tau-stable SY5Y cells with PARK8/LRRK2 antibody Cat. No.: AP13698PU-N (green; phosphorylated tau is red). Nuclear staining was performed with Dapi (blue). In WB, PARK8/LRRK2 was detected in mouse brain lysate with Cat.No. AM11057PU-N

Parkin (PARK2) is an E3 ligase in the ubiquitin-proteasome system and plays an important role in juvenile-onset PD. Malfunctions due to mutations in the PARK2 gene may lead to reduced degradation of proteins toxic to dopaminergic neurons. Phosphorylation of parkin at Ser101 and Ser378 may have an important regulatory role on its E3 ubiquitin ligase activity. Parkin has been shown to interact with SNCA, PARK8/LRRK2 and STUB1/CHIP (STIP1 homology and U-Box containing protein 1/C terminus of HSC70-interacting protein), which might contribute to PD development.

Parkin coregulated gene protein (PACRG) is a gene located close to parkin and thought to be co-transcribed with parkin. The PACRG protein is also a component of Lewy bodies in PD patients.

DJ-1/PARK7 participates in protection of neuronal cells from oxidative stress and mutation may lead to loss of this protection causing neuronal degradation. The roles of oxidative stress and mitochondrial dysfunction are under investigation as contributing factors to onset of PD.

Fig. 3: Human breast tissue (FFPE) stained with DJ-1/PARK7 antibody Cat.-No. AP15523PU-N

PTEN-induced putative kinase 1 (PINK1) is a mitochondrial serine/threo-nine-protein kinase thought to protect cells from stress-induced mitochon-drial dysfunction. Mutations in this gene may lead to early-onset PD.

Nuclear receptor-related factor 1 (NR4A2/NURR1) is a transcription factor expressed in the embryonic ventral midbrain. In developing and adult dopamine neurons, NR4A2 is required for the expression of several genes important for dopamine synthesis and function. Mutations are suggested to lead to dopaminergic dysfunction.

Synphilin 1 (SNCAIP), a substrate of parkin, interacts with alpha-synuclein and is observable in Lewy bodies. Mutation of the SNCAIP may lead to enhanced apoptosis. The function of synphilin 1 in PD susceptibility remains to be confirmed.

Alpha-crystallin B chain is a member of the small heat shock protein family and acts as a molecular chaperone preventing aggregation of denatured proteins and prevents apoptosis by inhibiting caspases. Enhanced expression of alpha-crystallin B chain is observed in numerous neuro-degenerative diseases such as Alzheimer's disease, multiple sclerosis and PD.



Key References

 
Gasser T, 1998, Nat Genet
 
Funayama M, 2002, Ann Neurol
 
Zimprich A, 2004, Neuron
 
Kitada T, 1998, Nature
 
Leroy E, 1998, Nature
 
van Duijn CM, 2001, Am J Hum Genet
 
Kawahara K, 2008, J Biol Chem
 
Yamamoto A, 2005, J Biol chem.
 
Le WD, 2003, Nat Genet
 
Marx FP,2003, Hum Mol Genet
 
Imai Y, 2002, Mol Cell
 
Renkawek, K, 1996, NeuroReport

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Primary Antibodies

Catalog No. Host Iso. Clone Pres. React. Applications  

Alpha-crystallin B chain / CRYA2 antibody

Immunohistochemical analysis of paraffin-embedded human brain hippocampus (A), lung cancer (B), brain tumor (C), breast cance (D), showing cytoplasmic localization with DAB staining using CRYAB antibody Cat.-No AM06212SU-N Mouse IgG2a 1D11C6E6 Ascites Hu E, P, WB
0.1 ml / €440.00
  Acris Antibodies GmbH

Alpha-crystallin B chain / CRYA2 antibody

Western blot analysis of AlphaB Crystallin in bovine cell lines using a 1:1000 dilution of the antibody Mouse IgG1 1A7.D5 Aff - Purified Bov, Hu E, P, WB
50 µg / €220.00
  Acris Antibodies GmbH

Alpha-crystallin B chain / CRYA2 antibody

Western blot analysis: Recombinant α-crystallin A (αA) and the extract of mouse eye (ME) were resolved by SDS-PAGE, transferred to PVDF membrane and probed with anti-human α-crystallin B antibody (1:1,000). Proteins were visualized using a goat anti-mouse secondary antibody conjugated to HRP and an ECL detection system. Mouse IgG2b 2E8 Purified Hu, Ms E, F, WB
50 µl / €230.00
  Acris Antibodies GmbH

Alpha-Synuclein / SNCA (also beta reactive) antibody

Flow cytometry analysis of α,β -Synuclein LNCaP cell line staining at 2-5ug for 1x106 cells (red line). The secondary antibody used goat anti mouse IgG mouse IgG Alexa fluor 488 conjugate Isotype control antibody was mouse IgG (black line). Mouse IgG1 3B6 Purified Hu, Ms, Rt E, F, ICC/IF, WB
50 µl / €230.00
  Acris Antibodies GmbH

Alpha-Synuclein / SNCA antibody

Human brain stained with Anti-alpha-Synuclein antibody Rabbit Purified Hu, Rt P
0.1 ml / €180.00
  Acris Antibodies GmbH

Alpha-Synuclein / SNCA pSer129 antibody

Figure 1. Western blot of rat cortex lysate showing specific labeling of the ~15 k alpha synuclein protein phosphorylated at Ser129. Immunolabeling is blocked by the phosphopeptide (peptide) used as antigen but not by the corresponding dephosphopeptide (not shown). Rabbit IgG Aff - Purified Bov, Can, Hu, Ms, non-Human Primates, Rt WB
0.1 ml / €380.00
  Acris Antibodies GmbH

DJ-1 / PARK7 antibody

Human breast stained with DJ-1 antibody Rabbit Purified Hu, Ms P, WB
0.1 ml / €190.00
  Acris Antibodies GmbH

DJ-1 / PARK7 antibody

Immunofluorescence of HeLa cells stained with anti-park7 (green) showing strong cytoplasmic staining and anti-vimentin antibody (red). Mouse IgG1 4H4 Purified Bov, Hu, Ms, Rt ICC/IF, WB
0.1 ml / €380.00
  Acris Antibodies GmbH

DJ-1 / PARK7 antibody

Western Blot analysis: Jurkat cell lysate was resolved by SDS-PAGE, transferred to PVDF membrane and probed with anti-Human Park7/DJ-1 Antibody Cat.-No SM6031 (1/1000). Protein was visualized using a Goat anti-Mouse secondary antibody conjugated to HRP and aN ECL detection system. Mouse IgG1 1B11 Purified Hu E, WB
50 µl / €230.00
  Acris Antibodies GmbH

Dopamine antibody

Dopamine Mouse IgG2b DA.2B11 Purified E, ICC/IF
0.1 mg / €350.00
  Acris Antibodies GmbH

NR4A2 antibody

Immunofluorescence of monoclonal antibody to NR4A2 on HeLa cell. [antibody concentration 10 ug/ml] Mouse IgG2a 4A6 Purified Hu E, ICC/IF, WB
0.1 mg / €370.00
  Abnova Taiwan Corp.

PACRG (204-215) antibody

Colon: Formalin-Fixed Paraffin-Embedded (FFPE) Rabbit Aff - Purified Chk, Hu, Rt, Ze E, ICC/IF, P, WB
50 µg / €470.00
  Acris Antibodies GmbH

PARK2 / Parkin pSer101 antibody

Figure 1. Western blot of HEK293 cells transfected with Parkin WT (Phospho) and Parkin S101 mutant (non-phospho) showing the phospho-specific immunolabeling of the ~ 52 k parkin protein.  The immunolabeling is absent in the Parkin S101 mutant. Rabbit IgG Aff - Purified Bov, Hu, non-Human Primates WB
0.1 ml / €380.00
  Acris Antibodies GmbH

PARK2 / Parkin pSer378 antibody

Figure 1. Western blot of HEK293 cells transfected with Parkin WT (Phospho) and Parkin S378 mutant (non-phospho) showing the phospho-specific immunolabeling of the ~52 k Parkin protein.  The immunolabeling is absent in the parkin S378 mutant. Rabbit IgG Aff - Purified Hu WB
0.1 ml / €380.00
  Acris Antibodies GmbH

PARK2 / Parkin antibody

AP15714PU Parkin antibody staining of Alzheimer's Brain. Rabbit Purified Hu, Ms, Rt P
0.1 ml / €180.00
  Acris Antibodies GmbH

PARK8 / LRRK2 (C-term) antibody

Figure 1. Western blot analysis of anti-LRRK2 Mab (Cat. #AM11057PU-N) to detect LRRK2 in mouse brain cell lysate. Mouse IgG1 133AT720 Purified Hu, Ms E, WB
0.4 ml / €370.00
  Acris Antibodies GmbH

PARK8 / LRRK2 (841-960) antibody

PARK8 / LRRK2 Mouse IgG2a S231B-34 Purified Hu, Rt ICC/IF, P, WB
0.1 mg / €380.00
  Acris Antibodies GmbH

PARK8 / LRRK2 antibody

Tau-stable SY5Y cell image stained for endogenous LRRK (green) by AP13698PU-N (affinity purified), phosphorylated tau (red, monoclonal AT8) and nuclear staining by DAPI. Rabbit Ig Purified Hu, Ms ICC/IF, WB
0.4 ml / €370.00
  Acris Antibodies GmbH

PINK1 (484-504) antibody

Testis: Formalin-Fixed Paraffin-Embedded (FFPE) Rabbit IgG Aff - Purified Bear, Bov, Bt, Can, Eq, Hst, Hu, Mky, Ms, Op, Por, Prim, Rb, Rt P, WB
50 µg / €470.00
  Acris Antibodies GmbH

PINK1 antibody

Formalin-fixed and paraffin-embedded human cancer tissue reacted with the primary antibody, which was peroxidase-conjugated to the secondary antibody, followed by AEC staining. Rabbit Ig Purified Hu E, P, WB
0.4 ml / €370.00
  Acris Antibodies GmbH

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