Neural cells are highly sensitive to defects in processes involved in ubiquitination of targeted proteins and subsequent degradation of those proteins via the ubiquitin proteasome system (UPS). A number of diseases associated with human genes with roles in ubiquitination processes have been modeled in Drosophila; these include diseases associated with the human gene UBE3A (FBhh0000081 and FBhh0000515), UBE2A (FBhh0000140), HUWE1 (FBhh0000141), UBA5 (FBhh0000613), and UBQLN2 (FBhh0000824).
Many of the most common neurodegenerative diseases are associated with accumulation of aggregated proteins that fail to be eliminated by the UPS. For example, the gene implicated in one of the subtypes of Parkinson disease is an E3 ubiquitin ligase (PRKN; see FBhh0000008). Even when not causative, UPS dysfunction may contribute to the development of these diseases.
Investigations in Drosophila have also used transgenes of the highly conserved ubiquitin 76-mer, including wild-type, missense variants, and modified forms; see the FlyBase gene report for Uuuu\Ub (species of origin unknown).
[updated Jul. 2018 by FlyBase; FBrf0222196]
Neural cells are highly sensitive to defects in processes of ubiquitination and degradation of ubiquitinated proteins via the ubiquitin proteasome system (UPS). UPS dysfunction has been reported in the most common neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. (reviewed in Atkin and Paulson, 2014, pubmed:25071440; Zheng et al., 2016, pubmed:28018215).
Components of the UPS are being investigated in the context of potential therapeutic targets that can be used to accelerate the clearance of disease-linked proteins (reviewed in Dantuma and Bott, 2014; pubmed:25132814).
