Yang, Cheng;
(2019)
The role of basal autophagy in oligodendrocyte development.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Neurodegenerative diseases can be caused by abnormal protein accumulation, mitochondrial dysfunction and intracellular oxidative stress, all of which fall within the realm of autophagy, including autophagic clearance of protein aggregates and autophagic degradation of organelles (e.g. mitophagy). Although the exact mechanisms regulating autophagy in the central nervous system (CNS) remain unknown, it is likely that autophagy failure plays a critical role in the pathology of neurodegenerative disease. This study investigates the role of basal autophagy in oligodendrocyte (OL) development and OL function, focusing on autophagic activity in OL lineage cells and the effect of autophagy on OL production during OL development and in adulthood. It has been reported that myelinophagy, a recently discovered form of selective autophagy, is involved in the degradation of myelin and promotes myelin clearance in the peripheral nervous system (PNS). My current study also examines the role of autophagy in myelination, which has not yet been well investigated. We generate mice lacking autophagy related gene 5 (Atg5) specifically in OL lineage cells to study the role of autophagy in OL development and OL function. Employing immunostaining, electron microscopy and lipidomics analysis, we found that although the loss of autophagy does not have an evident effect on the proliferation and differentiation of OL precursors during OL development, it can cause abnormal aggregations of intracellular proteins in adult-born OLs with age, indicating that autophagy primarily affects adult-born OL function. In addition, a number of astrocytes become reactive in the cortex of these mice, which is the hallmark in response to the CNS pathologies, hinting at the importance of OL autophagy in maintaining brain homeostasis.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The role of basal autophagy in oligodendrocyte development |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10086487 |
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