Proteasome activity and tau protein aggregation in Chinese hamster ovaries cell model
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1
Laboratory of Histology, Neuroanatomy and Neuropathology, ULB Neuroscience Institute (UNI), Belgium
The proteasome is one of the cellular entities involved in the catabolism of oxidized and misfolded proteins, its activity decreases during aging in parallel with the appearance of a lethal proteotoxicity for the cell. In neurodegenerative diseases an even more marked reduction in proteasome activity raises the question of its role as an aggravating cofactor in these pathologies.
Our work focuses on the causal link between decreased proteasome activity and aggregation of tau protein in tau pathologies such as Alzheimer's disease. Inhibition of the proteasome by specific inhibitors (lactacystin and MG132) on a CHO (Chinese hamster ovaries) cell model causes post-translational modifications like the increase of phosphorylated and misfolded forms of tau protein. In parallel with these modifications, kinds of aggregation or agresomes of tau protein are observed by Immunohistochemistry, these agresomes are not the result of a functional relay of the autophagy lysosome system but the consequence of a dysfunction of the protein quality control machinery (ubiquitin proteasome system).
The results of this work show the key role of proteasome dysfunction in the process of pathological aggregation of tau protein during tau pathologies, which supports the idea of exploiting proteasome reactivation as a therapeutic target in the treatment of neurodegenerative diseases such as Alzheimer's disease.
Acknowledgements
My sincere thanks to all the team of the laboratory of histology, neuroanatomy and neuropathology, especially to my promoter Professor Alain Boom for their welcome and their scientific support.
Keywords:
Proteasome,
tau protein,
Aggregation,
tau pathology,
Alzheiemr's disease
Conference:
Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018.
Presentation Type:
e-posters
Topic:
NOVEL STRATEGIES FOR NEUROLOGICAL AND MENTAL DISORDERS: SCIENTIFIC BASIS AND VALUE FOR PATIENT-CENTERED CARE
Citation:
Djerbib
S and
Boom
A
(2019). Proteasome activity and tau protein aggregation in Chinese hamster ovaries cell model.
Front. Neurosci.
Conference Abstract:
Belgian Brain Congress 2018 — Belgian Brain Council.
doi: 10.3389/conf.fnins.2018.95.00055
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Received:
22 Aug 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Mr. Sami Djerbib, Laboratory of Histology, Neuroanatomy and Neuropathology, ULB Neuroscience Institute (UNI), Brussels, Brussels, Belgium, samidjerbib@hotmail.com