title: Regulation of protein homeostasis in neurodegenerative diseases: the role of coding and non-coding genes.
abstract: Protein homeostasis is fundamental for cell function and survival, because proteins are involved in all aspects of cellular function, ranging from cell metabolism and cell division to the cell's response to environmental challenges. Protein homeostasis is tightly regulated by the synthesis, folding, trafficking and clearance of proteins, all of which act in an orchestrated manner to ensure proteome stability. The protein quality control system is enhanced by stress response pathways, which take action whenever the proteome is challenged by environmental or physiological stress. Aging, however, damages the proteome, and such proteome damage is thought to be associated with aging-related diseases. In this review, we discuss the different cellular processes that define the protein quality control system and focus on their role in protein conformational diseases. We highlight the power of using small organisms to model neurodegenerative diseases and how these models can be exploited to discover genetic modulators of protein aggregation and toxicity. We also link findings from small model organisms to the situation in higher organisms and describe how some of the genetic modifiers discovered in organisms such as worms are functionally conserved throughout evolution. Finally, we demonstrate that the non-coding genome also plays a role in maintaining protein homeostasis. In all, this review highlights the importance of protein and RNA homeostasis in neurodegenerative diseases.
authors.affiliation: European Research Institute for the Biology of Aging, University of Groningen, University Medical Centre Groningen, 9700 AD, Groningen, The Netherlands.|Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, 4099-003, Porto, Portugal.
authors.forename: Olga
authors.initials: O
authors.lastname: Sin
authors.affiliation: European Research Institute for the Biology of Aging, University of Groningen, University Medical Centre Groningen, 9700 AD, Groningen, The Netherlands. e.a.a.nollen@umcg.nl.
authors.forename: Ellen A A
authors.initials: EA
authors.lastname: Nollen
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D004195:Disease Models, Animal; D004330:Drosophila; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D010300:Parkinson Disease / Q000503:physiopathology; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology
chemical_list: D011506:Proteins; D022661:RNA, Untranslated
keywords: Aggresome; Alzheimer’s disease; C. elegans; Chaperone; Genetic modifiers; Huntington’s disease; JunQ; Neurodegeneration; Non-coding RNA; Parkinson’s disease; Protein aggregation; Protein homeostasis; Protein quality control; Proteostasis; Proteotoxicity; iPOD; miRNA; tRNA