Burtscher, Johannes; Pepe, Giuseppe; Maharjan, Niran; Riguet, Nathan; Di Pardo, Alba; Maglione, Vittorio; Millet, Grégoire P (2023). Sphingolipids and impaired hypoxic stress responses in Huntington disease. Progress in lipid research, 90, p. 101224. Elsevier 10.1016/j.plipres.2023.101224
|
Text
1-s2.0-S0163782723000140-main.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
Huntington disease (HD) is a debilitating, currently incurable disease. Protein aggregation and metabolic deficits are pathological hallmarks but their link to neurodegeneration and symptoms remains debated. Here, we summarize alterations in the levels of different sphingolipids in an attempt to characterize sphingolipid patterns specific to HD, an additional molecular hallmark of the disease. Based on the crucial role of sphingolipids in maintaining cellular homeostasis, the dynamic regulation of sphingolipids upon insults and their involvement in cellular stress responses, we hypothesize that maladaptations or blunted adaptations, especially following cellular stress due to reduced oxygen supply (hypoxia) contribute to the development of pathology in HD. We review how sphingolipids shape cellular energy metabolism and control proteostasis and suggest how these functions may fail in HD and in combination with additional insults. Finally, we evaluate the potential of improving cellular resilience in HD by conditioning approaches (improving the efficiency of cellular stress responses) and the role of sphingolipids therein. Sphingolipid metabolism is crucial for cellular homeostasis and for adaptations following cellular stress, including hypoxia. Inadequate cellular management of hypoxic stress likely contributes to HD progression, and sphingolipids are potential mediators. Targeting sphingolipids and the hypoxic stress response are novel treatment strategies for HD.
Item Type: |
Journal Article (Review Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Sahli Building > Forschungsgruppe Neurologie 04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
UniBE Contributor: |
Maharjan, Niran |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1873-2194 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
13 Mar 2023 12:52 |
Last Modified: |
13 May 2023 00:14 |
Publisher DOI: |
10.1016/j.plipres.2023.101224 |
PubMed ID: |
36898481 |
Uncontrolled Keywords: |
Huntington disease Sphingolipids conditioning hypoxia mitochondria |
BORIS DOI: |
10.48350/179906 |
URI: |
https://boris.unibe.ch/id/eprint/179906 |
Actions (login required)
 |
Edit item |