title: The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases.
abstract: OBJECTIVE
  HSPB8 is a small heat shock protein that forms a complex with the co-chaperone BAG3. Overexpression of the HSPB8-BAG3 complex in cells stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, whose accumulation is a hallmark of many neurodegenerative disorders. HSPB8-BAG3 could thus play a protective role in protein aggregation diseases and might be specifically upregulated in response to aggregate-prone protein-mediated toxicity. Here we analysed HSPB8-BAG3 expression levels in post-mortem human brain tissue from patients suffering of the following protein conformation disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3 (SCA3).
  
  
  METHODS
  Western blotting and immunohistochemistry techniques were used to analyse HSPB8 and BAG3 expression levels in fibroblasts from SCA3 patients and post-mortem brain tissues, respectively.
  
  
  RESULTS
  In all diseases investigated, we observed a strong upregulation of HSPB8 and a moderate upregulation of BAG3 specifically in astrocytes in the cerebral areas affected by neuronal damage and degeneration. Intriguingly, no significant change in the HSPB8-BAG3 expression levels was observed within neurones, irrespective of their localization or of the presence of proteinaceous aggregates.
  
  
  CONCLUSIONS
  We propose that the upregulation of HSPB8 and BAG3 may enhance the ability of astrocytes to clear aggregated proteins released from neurones and cellular debris, maintain the local tissue homeostasis and/or participate in the cytoskeletal remodelling that astrocytes undergo during astrogliosis.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Seidel
authors.forename: J
authors.initials: J
authors.lastname: Vinet
authors.forename: W F A den
authors.initials: WF
authors.lastname: Dunnen
authors.forename: E R
authors.initials: ER
authors.lastname: Brunt
authors.forename: M
authors.initials: M
authors.lastname: Meister
authors.forename: A
authors.initials: A
authors.lastname: Boncoraglio
authors.forename: M P
authors.initials: MP
authors.lastname: Zijlstra
authors.forename: H W G M
authors.initials: HW
authors.lastname: Boddeke
authors.forename: U
authors.initials: U
authors.lastname: Rüb
authors.forename: H H
authors.initials: HH
authors.lastname: Kampinga
authors.forename: S
authors.initials: S
authors.lastname: Carra
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D018832:Molecular Chaperones; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D017346:Protein Serine-Threonine Kinases