title: Molecular chaperone disorders: defective Hsp60 in neurodegeneration.
abstract: Chaperonins, a subgroup of molecular chaperones, form ring-shaped structures and assist folding of proteins by enclosing them in their inner cavity. The mitochondrial Hsp60/Hsp10 chaperonin system is essential for cell viability and only a very small number of mutations causing human disease have so far been found that appear to selectively affect neuronal tissues. We here review the knowledge on the mammalian Hsp60/Hsp10 system and discuss evidence and observations, which may explain why this is the case. The Hsp60 mutations shown to be associated with neurodegenerative diseases mildly affect the protein and leave residual function. We present arguments for the notion that the neuron/glia specificity may be due to an effect of Hsp60 deficiency on myelination, a neuron-specific property. The substrates of the Hsp60/Hsp10 system are only poorly defined, but the combination of deficiency of a number of mitochondrial enzymes and proteins that are highly dependent on this system for folding is the likely trigger for deficient myelination. However, a number of experimental observations indicate that Hsp60 may also have roles outside mitochondria and deficiency of Hsp60 due to mutation may also affect myelination via these signaling pathways. Taken together, it appears that mild Hsp60 deficiency primarily affects neuronal and/or glia cells whereas more severe deficiency of Hsp60 would affect all tissues and not be compatible with life. We discuss in the end what approaches may lead to a further understanding of the functions of the Hsp60/Hsp10 system in mammalian cells and thus its role in disease conditions.
authors: Research Unit for Molecular Medicine, Department of Clinical Medicine, HEALTH, Aarhus University and Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. peter.bross@ki.au.dk
authors: Peter
authors: P
authors: Bross
authors: Raffaella
authors: R
authors: Magnoni
authors: Anne Sigaard
authors: AS
authors: Bie
mesh_terms: D000818:Animals; D018835:Chaperonin 10 / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D017510:Protein Folding; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; C060293:HSPD1 protein, human; C557066:Hspd1 protein, mouse; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones