Protein aggregation and degradation mechanisms in neurodegenerative diseases
- PMID: 23516262
- PMCID: PMC3601466
Protein aggregation and degradation mechanisms in neurodegenerative diseases
Abstract
Neurodegenerative diseases are characterized by selective neuronal vulnerability and neurodegeneration in specific brain regions. The pathogenesis of these disorders centrally involves abnormal accumulation and aggregation of specific proteins, which are deposited in intracellular inclusions or extracellular aggregates that are characteristic for each disease. Increasing evidence suggests that genetic mutations or environmental factors can instigate protein misfolding and aggregation in these diseases. Consequently, neurodegenerative diseases are often considered as conformational diseases. This idea is further supported by studies implicating that impairment of the protein quality control (PQC) and clearance systems, such as the ubiquitin-proteasome system and autophagosome-lysosome pathway, may lead to the abnormal accumulation of disease-specific proteins. This suggests that similar pathological mechanisms may underlie the pathogenesis of the different neurodegenerative disorders. Interestingly, several proteins that are known to associate with neurodegenerative diseases have been identified as important regulators of PQC and clearance systems. In this review, we summarize the central features of abnormal protein accumulation in different common neurodegenerative diseases and discuss some aspects of specific disease-associated proteins regulating the PQC and clearance mechanisms, such as ubiquilin-1.
Keywords: IPOD; JUNQ; Protein quality control; aggresome; autophagy; inclusion body; neurodegenerative diseases; protein misfolding; ubiquilin-1; ubiquitin-proteasome system.
Figures
Similar articles
-
Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation.Biochem Soc Trans. 2010 Feb;38(Pt 1):150-5. doi: 10.1042/BST0380150. Biochem Soc Trans. 2010. PMID: 20074050 Review.
-
Does impairment of the ubiquitin-proteasome system or the autophagy-lysosome pathway predispose individuals to neurodegenerative disorders such as Parkinson's disease?J Alzheimers Dis. 2010;19(1):1-9. doi: 10.3233/JAD-2010-1231. J Alzheimers Dis. 2010. PMID: 20061621 Review.
-
The role of autophagy in age-related neurodegeneration.Neurosignals. 2008;16(1):75-84. doi: 10.1159/000109761. Epub 2007 Dec 5. Neurosignals. 2008. PMID: 18097162 Review.
-
Molecular pathogenesis of protein misfolding diseases: pathological molecular environments versus quality control systems against misfolded proteins.J Biochem. 2009 Dec;146(6):751-6. doi: 10.1093/jb/mvp119. Epub 2009 Jul 30. J Biochem. 2009. PMID: 19643812 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
Cited by 68 articles
-
Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases.Front Physiol. 2020 Jul 2;11:694. doi: 10.3389/fphys.2020.00694. eCollection 2020. Front Physiol. 2020. PMID: 32714204 Free PMC article. Review.
-
Oxidative Damage of Blood Platelets Correlates with the Degree of Psychophysical Disability in Secondary Progressive Multiple Sclerosis.Oxid Med Cell Longev. 2020 Jun 17;2020:2868014. doi: 10.1155/2020/2868014. eCollection 2020. Oxid Med Cell Longev. 2020. PMID: 32655763 Free PMC article.
-
Role of Exosomes in Cancer-Related Cognitive Impairment.Int J Mol Sci. 2020 Apr 15;21(8):2755. doi: 10.3390/ijms21082755. Int J Mol Sci. 2020. PMID: 32326653 Free PMC article. Review.
-
Drosophila NUAK functions with Starvin/BAG3 in autophagic protein turnover.PLoS Genet. 2020 Apr 22;16(4):e1008700. doi: 10.1371/journal.pgen.1008700. eCollection 2020 Apr. PLoS Genet. 2020. PMID: 32320396 Free PMC article.
-
Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review.Brain Sci. 2020 Apr 11;10(4):232. doi: 10.3390/brainsci10040232. Brain Sci. 2020. PMID: 32290481 Free PMC article. Review.
LinkOut - more resources
-
Full Text Sources
-
Molecular Biology Databases