caa a22 4500 606177337 CHVBK 20210128100751.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00018-015-1985-0 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1985-0 Regulation of protein homeostasis in neurodegenerative diseases: the role of coding and non-coding genes [Elektronische Daten] [Olga Sin, Ellen Nollen] 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. The Author(s), 2015 Protein homeostasis nationallicence Genetic modifiers nationallicence Non-coding RNA nationallicence Protein aggregation nationallicence Neurodegeneration nationallicence Alzheimer's disease nationallicence Parkinson's disease nationallicence Huntington's disease nationallicence C. elegans nationallicence Proteotoxicity nationallicence Protein quality control nationallicence Proteostasis nationallicence tRNA nationallicence iPOD nationallicence JunQ nationallicence Aggresome nationallicence Chaperone nationallicence miRNA nationallicence Sin Olga European Research Institute for the Biology of Aging, University of Groningen, University Medical Centre Groningen, 9700 AD, Groningen, The Netherlands aut Nollen Ellen European Research Institute for the Biology of Aging, University of Groningen, University Medical Centre Groningen, 9700 AD, Groningen, The Netherlands aut Cellular and Molecular Life Sciences Springer Basel 72/21(2015-11-01), 4027-4047 1420-682X 72:21<4027 2015 72 18 https://doi.org/10.1007/s00018-015-1985-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1985-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sin Olga European Research Institute for the Biology of Aging, University of Groningen, University Medical Centre Groningen, 9700 AD, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Nollen Ellen European Research Institute for the Biology of Aging, University of Groningen, University Medical Centre Groningen, 9700 AD, Groningen, The Netherlands aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/21(2015-11-01), 4027-4047 1420-682X 72:21<4027 2015 72 18