title: Protein quality control in neurodegeneration: walking the tight rope between health and disease.
abstract: Most neurodegenerative disorders are characterised by deposits of aggregated proteins that are readily visualised by light microscopy. Although the presence of such a bulky structure inside the cell or in the extracellular space is likely not to be healthy, over recent years the idea has emerged that these end-stage aggregates are a relatively safe way to deposit harmful aberrant proteins. Protein quality control is a multi-level security system to safeguard cells from aberrant proteins and is therefore a protective response. However, protein quality control may turn destructive in case of impairment of protein quality control for example by aging or because of overflow of the quality control systems due to prolonged exposure. In many cases the medicine is worse than the cause and the "protective" response of the cell to aggregates kills the cell, rather than the aggregate itself. Here we review the role of protein quality control in neurodegeneration and aim to distinguish protective and destructive responses to aggregates in order to find targets for therapeutic intervention.
authors.affiliation: Research group Cellular Quality Control, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. e.hol@nin.knaw.nl
authors.forename: E M
authors.initials: EM
authors.lastname: Hol
authors.forename: W
authors.initials: W
authors.lastname: Scheper
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism* / Q000503:physiopathology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding
chemical_list: D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D046988:Proteasome Endopeptidase Complex