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The emerging importance of ubiquitination regulators in cancer therapy
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).
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:
(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).
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).
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.
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