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- Rostami, Jinar, 1992-
(författare)
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The role of glial cells in alpha-synuclein pathology : Focus on degradation, cell-to-cell propagation and inflammation
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Growing evidence emphasizes the role of astrocytes and microglia in Parkinson’s disease (PD) and Alzheimer’s disease (AD). Yet, little is known about their impact on specific disease processes and if their involvement is beneficial or detrimental. The aim of this thesis was to further investigate the role of astrocytes and microglia in PD and AD. To this purpose, cultured human astrocytes and microglia were exposed to aggregates of alpha-synuclein (αSYN) or amyloid-beta (Aβ), proteins that are central to PD and AD brain pathology, respectively.In Paper I, the toxicity and cell-to-cell spreading of aggregated αSYN in human astrocytes were evaluated. We found that astrocytes can engulf large amounts of αSYN aggregates, which are stored inside the cells instead of being degraded. This intracellular storage was found to result in severe cellular stress. As a response, stressed astrocytes were shown to transfer αSYN via tunneling nanotubes (TNT) to healthy astrocytes.T cells have been observed to enter the PD brain, but little is known about which stationary cell types they interact with. In Paper II, the ability of astrocytes and microglia to act as antigen presenting cells in the presence of aggregated αSYN was investigated. Both astrocytes and microglia were capable of expressing major histocompatibility class I (MHCI) and MHCII. However, only astrocytes had the capacity to express other molecules crucial for T-cell activation, such as CD80 and CD86. MHCII expressing astrocytes were also found in close vicinity to T cells in the PD brain.In paper III, the cross-talk between microglia and astrocytes in the presence of αSYN and Aβ aggregates was examined. When cultured separately, microglia appeared to degrade αSYN and Aβ better than astrocytes. However, co-culture experiments showed that microglia and astrocytes have a synergistic effect on the clearance of protein aggregates. Cell-to-cell contact was revealed as one of the possible mechanisms by which astrocytes and microglia communicate with each other.In Paper IV, the molecular mechanisms by which the compound KYP-2407 enhances αSYN clearance was investigated. We found that KYP-2407 stimulates the auto-lysosomal pathway in the presence of αSYN aggregates. Calpain proteins, which increase αSYN aggregation and diminish autophagy in PD, were also shown to be reduced in the presence of KYP-2407.Taken together, this thesis contributes with novel and important knowledge to the potential role of astrocytes and microglia in PD and AD.
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| 2. |
- Karlsson, Louise, 1989-, et al.
(författare)
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Taking control of one's everyday life - a qualitative study of experiences described by participants in an occupational intervention
- 2023
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Ingår i: BMC Public Health. - London : BioMed Central (BMC). - 1471-2458. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sick leave due to stress-related ill-health is increasing and is often caused by occupational imbalance. These types of issues tend to affect both the ability to work and cope with everyday life, as well as the overall experience of health, negatively. There is still little knowledge on how to prepare people and workplaces for the return-to-work process after participation in a work rehabilitation program due to stress and occupational ill-health. Therefore, this study aimed to describe what is needed to achieve a balanced everyday life that includes paid work as experienced by individuals who had participated in a ReDO® intervention due to occupational imbalance and ill-health. METHODS: The concluding notes from 54 informants' medical records were used for qualitative content analysis. The informants had participated in an occupational therapy group intervention to promote occupational health and regain full work capacity. RESULTS: The analysis resulted in one major theme and four categories describing how the informants perceive that they must take control of their everyday life as a whole. By doing so, they need to work with structurization and prioritization, social interaction, boundary setting, and occupational meaningfulness. CONCLUSION: The study indicates a highly relational process, where it is impossible to divide life into private and work, and presupposes balance in everyday life in multiple dimensions. Its contribution includes the formulation of perceived needs in the transition between intervention and return to work and could, through further research, be used to generate a more effective and sustainable return- and rehabilitation models. © 2023. The Author(s).
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