AIMS: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.

The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases / Seidel, K; Vinet, Jonathan; den Dunnen, Wfa; Brunt, Er; Meister, M; Boncoraglio, A; Zijlstra, Mp; Boddeke, Hwgm; Rüb, U; Kampinga, Hh; Carra, Serena. - In: NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY. - ISSN 0305-1846. - ELETTRONICO. - 38(1)(2012), pp. 39-53. [10.1111/j.1365-2990.2011.01198.x]

The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases.

VINET, JONATHAN;CARRA, Serena
2012

Abstract

AIMS: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.
38(1)
39
53
The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases / Seidel, K; Vinet, Jonathan; den Dunnen, Wfa; Brunt, Er; Meister, M; Boncoraglio, A; Zijlstra, Mp; Boddeke, Hwgm; Rüb, U; Kampinga, Hh; Carra, Serena. - In: NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY. - ISSN 0305-1846. - ELETTRONICO. - 38(1)(2012), pp. 39-53. [10.1111/j.1365-2990.2011.01198.x]
Seidel, K; Vinet, Jonathan; den Dunnen, Wfa; Brunt, Er; Meister, M; Boncoraglio, A; Zijlstra, Mp; Boddeke, Hwgm; Rüb, U; Kampinga, Hh; Carra, Serena
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/707750
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