PGP 9.5 Antibodies

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Recent blog

The emerging importance of ubiquitination regulators in cancer therapy

For Alzheimer's and Parkinson's Disease Research

Protein gene product (PGP) 9.5, also referred to as ubiquitin carboxy-terminal hydrolase L1 (UCHL1), is a deubiquitinating enzyme with both hydrolase and ligase activity. Its function is to bind and stabilize monoubiquitin, hydrolyze polyubiquitin, and carry out additional ubiquitinylation of ubiquitinylated proteins (Osaka et al. 2003).

Tissue Expression
 

As PGP9.5/UCHL1 is highly expressed in neurons, it is used to identify peripheral nervous system (PNS) axons. It can be found in neurons of the:

  • Sensory ganglia
  • Sympathetic ganglia
  • Enteric nervous system
  • Retina
  • Spermatogonia and sertoli cells
  • Trigeminal ganglia
  • Dorsal root ganglia

(Calzada et al. 1994, Kent and Clarke 1991, Wilson et al. 1988, Krammer et al. 1993, Phillips et al. 2004, Wang et al. 2018).

It can also be detected in murine embryos from day 10.5 onwards (Sidebotham et al. 2001, Sekiguchi et al. 2003).

Small Fibre Neuropathy
 

A key characteristic of PGP9.5/UCHL1 is its presence in neuronal projections in addition to the cell body. This feature makes it useful in developmental studies and investigations into cutaneous innervation (Dalsgaard et al. 1989, Karanth et al. 1991). Antibodies to PGP9.5/UCHL1 are therefore key tools for diagnosing small fibre neuropathy (SFN). SFN can be associated with pre-diabetes status and immune-mediated diseases, but is frequently of unknown aetiology. A common symptom is neuropathic pain (Devigili et al. 2008). PGP9.5/UCHL1 is also used to aid the diagnosis of fibromyalgia (Levine and Saperstein 2015).

Neurodegenerative Diseases
 

Proteomic analyses have shown PGP9.5/UCHL1 is subjected to oxidative modification in Alzheimer's disease (AD) and Parkinson's disease (PD). The oxidation of cysteine and methionine residues, and carbonyl formation reduces the solubility of PGP9.5/UCHL1 (Choi et al. 2004, Butterfield et al. 2006). Accumulation of insoluble PGP9.5/UCHL1 was accompanied by increases in tau tangles (de Vrij et al. 2004, Donovan et al. 2012).

This was also seen in the Aβ overproducing murine APP/PS1 animal model of Alzheimer's disease. The proportions of soluble to insoluble PGP9.5/UCHL1 were similar to that observed in human Alzheimer's disease brains. Additionally, an approximately 20% reduction in hydrolytic activity (in vitro) was reported (Gong et al. 2006).

In Parkinson’s disease two mutations have been suggested to be linked to the familial version of PD (Andersson et al. 2011). The I93M mutation has been linked to an increased risk of Parkinson’s disease, while the S18Y mutant seems to be neuroprotective. However, the evidence is inconclusive so far (Day and Thompson 2010, Ragland et al. 2009).

To support research that deepens the understanding of PGP9.5/UCHL1 in neurodegenerative diseases, and aids the diagnosis of complex conditions such as fibromyalgia, Bio-Rad supplies a range of antibodies against PGP9.5/UCHL1. These are found in the table below, which connects you to the product datasheets and the peer reviewed publications where the antibodies have been used. The monoclonal antibodies listed below are the highest cited clones for research into PGP9.5/UCHL1.

Anti-PGP 9.5 antibodies

    DescriptionSpecificityTargetFormatHostIsotypeClone Applications Citations Product Type Code


    References

    • Andersson FI et al. (2011). The effect of Parkinson's-disease-associated mutations on the deubiquitinating enzyme UCH-L1. J Mol Biol 407, 261–272.
    • Butterfield DA et al. (2006). Redox proteomics identification of oxidatively modified brain proteins in inherited Alzheimer's disease: an initial assessment. J Alzheimers Dis 10, 391–397.
    • Calzada B et al. (1994). Distribution of protein gene product 9.5 (PGP 9.5) immunoreactivity in the dorsal root ganglia of adult rat. Ann Anat 176(5), 437–441.
    • Choi J et al. (2004). Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases. J Biol Chem 279, 13256–13264.
    • Dalsgaard CJ et al. (1989). Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry 92(5), 385–390.
    • Day IN and Thompson RJ (2010). UCHL1 (PGP 9.5): neuronal biomarker and ubiquitin system protein. Prog Neurobiol 90, 327–362.
    • Devigili G et al. (2008). The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain 131, 1912-1925.
    • de Vrij FM et al. (2004). Protein quality control in Alzheimer's disease by the ubiquitin proteasome system. Prog Neurobiol 74, 249–270.
    • Donovan LE et al. (2012). Analysis of a membrane-enriched proteome from postmortem human brain tissue in Alzheimer's disease. Proteomics Clin Appl 6, 201–211.
    • Gong B et al. (2006). Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell 126, 775–788.
    • Karanth SS et al. (1991). An immunocytochemical study of cutaneous innervation and the distribution of neuropeptides and protein gene product 9.5 in man and commonly employed laboratory animals. Am J Anat 191(4), 369–383.
    • Kent C and Clarke PJ. (1991). The immunolocalisation of the neuroendocrine specific protein PGP9.5 during neurogenesis in the rat. Brain Res Dev Brain Res 58(1), 147–150.
    • Krammer HJ et al. (1993). Immunohistochemical visualization of the enteric nervous system using antibodies against protein gene product (PGP) 9.5. Ann Anat 175(4), 321–325.
    • Levine TD and Saperstein DS (2015). Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients. Clin Rheumatol 34(3), 413–417. PMID: 25535201
    • Osaka H. et al. (2003). Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet 12(16), 1945-58.
    • Phillips RJ et al. (2004). Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers. J Neurosci Methods 133 (1–2), 99–107.
    • Ragland M et al. (2009). Association between the ubiquitin carboxyl-terminal esterase L1 gene (UCHL1) S18Y variant and Parkinson's Disease: a HuGE review and meta-analysis. Am J Epidemiol 170, 1344–1357.
    • Sekiguchi S et al. (2003). Immunohistochemical analysis of protein gene product 9.5, a ubiquitin carboxyl-terminal hydrolase, during placental and embryonic development in the mouse. Exp Anim 52(4), 365–369.
    • Sidebotham EL et al. (2001). Assessment of protein gene product 9.5 as a marker of neural crest-derived precursor cells in the developing enteric nervous system. Pediatr Surg Int 17(4), 304–307.
    • Wang H et al. (2018). Transcriptional regulation of P63 on the apoptosis of male germ cells and three stages of spermatogenesis in mice. Cell Death Dis 9(2), 76.
    • Wilson PO et al. (1988). The immunolocalization of protein gene product 9.5 using rabbit polyclonal and mouse monoclonal antibodies. Br J Exp Pathol 69(1), 91–104.