title: DNAJ proteins and protein aggregation diseases.
abstract: Many neurodegenerative diseases are late onset diseases, associated with aggregation of proteins, implying that aged cells are more susceptible to proteotoxic stress. It is known that with aging, there is a decline in the functionality of chaperone networks and on the other hand, accumulation of damaged proteins occurs. Together, this has a cumulative effects on cellular protein homeostasis. Several studies have revealed that availability of DNAJ proteins, the co-chaperones to the Hsp70 machine, could be a rate-limiting factor in handling diseased proteins within the cell. In this review,we highlight how DNAJ proteins can affect aggregation of disease-causing proteins, if and how this depends on their function as Hsp70 co-chaperones, and how much this depends on the type of protein causing the disease. Finally, we will discuss the five known degenerative diseases that are linked to mutations in individual DNAJ members and what mechanism may underlie these DNAJ chaperonopathies.
authors: University of Groningen, University Medical Center Groningen, Department of Cell Biology, Groningen, The Netherlands.
authors: Vaishali
authors: V
authors: Kakkar
authors: Louis C B
authors: LC
authors: Prins
authors: Harm H
authors: HH
authors: Kampinga
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism
chemical_list: C494639:Dnaja1 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides; C097188:polyglutamine