Regulation of protein homeostasis in neurodegenerative diseases: the role of coding and non-coding genes

Alvarenga Fernandes Sin, O. & Nollen, E. A. A., Nov-2015, In : Cellular and molecular life sciences. 72, 21, p. 4027-4047 21 p.

Research output: Contribution to journalReview articleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)4027-4047
Number of pages21
JournalCellular and molecular life sciences
Issue number21
Publication statusPublished - Nov-2015


  • Protein homeostasis, Genetic modifiers, Non-coding RNA, Protein aggregation, Neurodegeneration, Alzheimer's disease, Parkinson's disease, Huntington's disease, C. elegans, Proteotoxicity, Protein quality control, Proteostasis, tRNA, iPOD, JunQ, Aggresome, Chaperone, miRNA, CENTRAL-NERVOUS-SYSTEM, CHAPERONE-MEDIATED AUTOPHAGY, RETICULUM-ASSOCIATED DEGRADATION, NUCLEOTIDE EXCHANGE FACTOR, ER-ASSOCIATED DEGRADATION, AMYLOID FIBRIL FORMATION, ALPHA-SYNUCLEIN BIOLOGY, HEAT-SHOCK RESPONSE, AGE-RELATED DECLINE, ENDOPLASMIC-RETICULUM

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