Ubiquitin proteasome system as a pharmacological target in neurodegeneration
- PMID: 17009921
- DOI: 10.1586/14737175.6.9.1337
Ubiquitin proteasome system as a pharmacological target in neurodegeneration
Abstract
Ubiquitinated protein aggregates are observed in the brains of Alzheimer's, Parkinson's and Huntington's disease patients and in other neurodegenerative disorders. These aggregates indicate that the ubiquitin proteasome system may be impaired in these diseases. To date no therapy is available that specifically targets this system, although preventing aggregate formation or stimulating the degradation of already formed aggregates by targeting components of the ubiquitin proteasome system is an attractive therapeutic approach. Here, we review the role of the ubiquitin proteasome system in aggregate formation with respect to neurodegenerative diseases, discussing the unfolded protein response, endoplasmic reticulum-associated degradation, aggresome formation and accumulation as well as aggregation and neurotoxicity of proteins involved in neurodegeneration. The potential of pharmacological intervention within this system in patients suffering from neurodegenerative diseases will be evaluated.
Similar articles
-
The ubiquitin-proteasome pathway in Parkinson's disease and other neurodegenerative diseases.Trends Cell Biol. 2004 Dec;14(12):703-11. doi: 10.1016/j.tcb.2004.10.006. Trends Cell Biol. 2004. PMID: 15564047 Review.
-
A single amino acid substitution in a proteasome subunit triggers aggregation of ubiquitinated proteins in stressed neuronal cells.J Neurochem. 2004 Jul;90(1):19-28. doi: 10.1111/j.1471-4159.2004.02456.x. J Neurochem. 2004. PMID: 15198663
-
Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders.J Neurol Sci. 2007 Jun 15;257(1-2):221-39. doi: 10.1016/j.jns.2007.01.033. Epub 2007 Apr 25. J Neurol Sci. 2007. PMID: 17462670 Review.
-
The aggravating role of the ubiquitin-proteasome system in neurodegeneration.FEBS Lett. 2005 Jan 31;579(3):571-6. doi: 10.1016/j.febslet.2004.12.058. FEBS Lett. 2005. PMID: 15670810 Review.
-
Dysfunction of the ubiquitin-proteasome system in multiple disease conditions: therapeutic approaches.Bioessays. 2008 Nov;30(11-12):1172-84. doi: 10.1002/bies.20852. Bioessays. 2008. PMID: 18937370 Review.
Cited by
-
Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications.Apoptosis. 2010 Nov;15(11):1292-311. doi: 10.1007/s10495-010-0466-z. Apoptosis. 2010. PMID: 20131003 Free PMC article. Review.
-
Targeting the integrated networks of aggresome formation, proteasome, and autophagy potentiates ER stress‑mediated cell death in multiple myeloma cells.Int J Oncol. 2015 Feb;46(2):474-86. doi: 10.3892/ijo.2014.2773. Epub 2014 Nov 24. Int J Oncol. 2015. PMID: 25422130 Free PMC article.
-
Protein quality control in neurodegeneration: walking the tight rope between health and disease.J Mol Neurosci. 2008;34(1):23-33. doi: 10.1007/s12031-007-0013-8. Epub 2007 Mar 24. J Mol Neurosci. 2008. PMID: 18157655 Review.
-
Relationships between diabetes and cognitive impairment.Endocrinol Metab Clin North Am. 2014 Mar;43(1):245-67. doi: 10.1016/j.ecl.2013.09.006. Epub 2013 Dec 12. Endocrinol Metab Clin North Am. 2014. PMID: 24582101 Free PMC article. Review.
-
A chemical compound commonly used to inhibit PKR, {8-(imidazol-4-ylmethylene)-6H-azolidino[5,4-g] benzothiazol-7-one}, protects neurons by inhibiting cyclin-dependent kinase.Eur J Neurosci. 2008 Nov;28(10):2003-16. doi: 10.1111/j.1460-9568.2008.06491.x. Eur J Neurosci. 2008. PMID: 19046382 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
