Endosomal Sorting Complex Required for Transport (ESCRT): Investigation of the expression and functional roles in neurodegenerative diseases

Endosomal Sorting Complex Required for Transport (ESCRT) is responsible for trafficking of misfolded proteins, unwanted organelles and ubiquitinated proteins to be degraded by lysosome. Abnormalities in ESCRT proteins have been linked to various neurodegenerative diseases such as Alzheimer's disease (AD), Huntington's disease, Parkinson's and Motor Neurone disease (MND). This study investigated the expression of ESCRT proteins in age matched nonneurodegenerative brains, AD brains, MND brains and spinal cord. The levels of ESCRT proteins in MND and AD brains are significantly different relative to age matched brains. The expression of TSG101 is markedly decreased in MND brains, spinal cord, and AD brains in comparison with control. Also, the level of VPS37A&B in MND is lower than in control brains and spinal cord but unchanged in AD brains. While the expression of CHMP2B significantly increased in MND brains and spinal cord, and noticeably reduced in AD brains when compared to control. Furthermore, there are differences in other ESCRT proteins e.g. STAM1 and ALIX. Expression of ESCRT proteins was recapitulated in MND cellular models such as NCS-34 cells using tunicamycin treatment. Altering the expression of TSG101 and CHMP2B demonstrated changes in TDP-43 and mTOR expression including altered autophagy markers such as LC3B and p62. Finally, knockout of SOCS3 enhances autophagy via TBK1 stabilisation. Conclusion: alterations in the expression of ESCRT proteins and SOCS3 may have a role in the pathogenesis of MND and could be new therapeutic targets for treating neurodegenerative diseases.

Grantor dc:publisher.institution

University of Bradford

Author dc:creator

• Mohamed, Laila A.A.H.

Advisors dc:contributor.advisor

• Kantamneni, Sriharsha
• Williamson, Ritchie

• Endosomal sorting complex required for transport (ESCRT)
• ESCRT proteins
• Neurodegenerative diseases
• Alzheimer's disease
• Motor neurone disease
• TSG101
• CHMP2B
• Western blot
• NCS-43 cells
• TBK1
• SOCS3
• Primary neuronal cells

Statement dc:rights

• <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

Language dc:language.iso

en

Repository record dc:identifier.uri

https://bradscholars.brad.ac.uk/handle/10454/20924

OAI identifier oai:identifier

oai:bradscholars.brad.ac.uk:10454/20924