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Proteasome inhibition leads to early loss of synaptic proteins in neuronal culture

  • Basic Neurosciences, Genetics and Immunology - Original Article
  • Published:
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An Erratum to this article was published on 05 June 2013

Abstract

A dysfunctional ubiquitin proteasome system may be a mediating factor of disease progression in Lewy body dementia (LBD). The effects of proteasome inhibition using lactacystin and epoxomicin in primary neuronal culture were studied to assess the validity of this model to reflect the cortical pathology of LBD. Treatment of primary cortical neurons with 5 μM lactacystin for 24 h led to a 38 % reduction in the levels of β-III-tubulin (p < 0.05), a 48 % reduction in the levels of synaptophysin (p < 0.05) and a 74 % reduction in the levels of drebrin (p < 0.01), when compared to controls. Results for epoxomicin were similar. The loss of neuronal protein occurred prior to any loss of mitochondrial activity or cell death. The results are reflective of the loss of synapses and the synaptic changes observed in LBD, which may be an early event in the neurodegeneration of LBD. The similarities with the pathological changes in LBD highlight the possibility that this model can potentially provide a platform to test novel treatments.

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Acknowledgments

This work was funded by the Edmond J. Safra Philanthropic Foundation.

Conflict of interest

The authors do not have any conflicts of interest relating to this work.

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Authors and Affiliations

  1. Wolfson Centre for Age Related Diseases, Guy’s Campus, King’s College London, St. Thomas Street, London, SE1 1UL, UK

    Natasha Bajic, Clive G. Ballard & Paul T. Francis

  2. Institute of Pharmaceutical Science, Hodgkin Building Guy’s Campus, King’s College London, London, SE1 1UL, UK

    Peter Jenner

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  1. Natasha Bajic
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  2. Peter Jenner
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  3. Clive G. Ballard
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  4. Paul T. Francis
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Correspondence to Clive G. Ballard.

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Bajic, N., Jenner, P., Ballard, C.G. et al. Proteasome inhibition leads to early loss of synaptic proteins in neuronal culture. J Neural Transm 119, 1467–1476 (2012). https://doi.org/10.1007/s00702-012-0816-9

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  • DOI: https://doi.org/10.1007/s00702-012-0816-9

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