Disease Associations Sample Clauses

Disease Associations. As one of the first identified substrates of xxxxxx (Imai et al. 2001), GPR37, alternatively named the xxxxxx-associated endothelin receptor-like receptor (PaelR), has been extensively studied for its potential role in Xxxxxxxxx’x disease. Xxxxxx is an E3 ubiquitin ligase whose function is to target misfolded proteins for degradation via the proteasome. Mutations in xxxxxx resulting in a loss-of-function (LOF) exacerbate dopaminergic neuron cell death by allowing misfolded protein accumulation and aggregation (Imai, Soda, and Takahashi 2000; Shimura et al. 2000; Zhang et al. 2000). Indeed, LOF mutations in xxxxxx result in the early-onset form of parkonsinism known as autosomal recessive juvenile parkinsonism (AR-JP) (Xxxxxxxx and Youle 2015). Misfolded GPR37 is found in the brains of individuals with AR-JP (Imai et al. 2001) and enriched within the Lewy bodies from individuals with Xxxxxxxxx’x disease, implicating GPR37 in parkinsonism pathogenesis (Murakami et al. 2004). While aggregation of misfolded GPR37 probably contributes to dopaminergic cell death, the loss of GPR37 function may also be detrimental. In addition to Xxxxxxxxx’x disease, GPR37 has been associated with several other disorders. For instance, GPR37 was identified as a differentially expressed gene in human samples from subjects with either bipolar disorder or major depressive disorder, as GPR37 mRNA was found to be upregulated in bipolar disorder and downregulated in major depressive disorder (Tomita et al. 2013). Likewise, the gene for GPR37 was found within the first autism spectrum disorder (ASD) locus identified, AUT1. Several mutations in GPR37 have been associated with autism (Fujita-Jimbo et al. 2012; Tanabe et al. 2015), but a definitive role for GPR37 in ASD has not been identified. GPR37 has also been implicated as contributing to peritoneal metastasis of gastric cancer (Wang et al. 2016) and is associated with several other forms of cancer (Toyota et al. 2001; Junaid et al. 2011; Liu, Zhu, et al. 2014).
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