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Title: Therapeutic and immunomodulatory functions of the translocator protein in Alzheimer's disease
Authors: Fairley, Lauren H.
Keywords: Science::Medicine
Issue Date: 2022
Publisher: Nanyang Technological University
Source: Fairley, L. H. (2022). Therapeutic and immunomodulatory functions of the translocator protein in Alzheimer's disease. Doctoral thesis, Nanyang Technological University, Singapore.
Abstract: Alzheimer’s disease (AD) is an age-associated neurodegenerative disease with no effective treatments. The translocator protein (TSPO) has been identified as a promising therapeutic target in AD, as TSPO ligands reduce the accumulation of beta-amyloid. However, the role of TSPO in other aspects of AD pathology, such as tauopathy, neuroinflammation, and mitochondrial dysfunction has not been explored. In this study, we report that treatment with TSPO ligands attenuates brain atrophy and neuroinflammation, but does not effect phosphorylated tau in the rTg4510 mouse model of tauopathy. Using the APP-KI nl-g-f mouse model with TSPO-KO, we show that TSPO-KO increases amyloid load, reduces phagocytic microglia, and protective microglial subpopulations. Lastly, treatment with TSPO ligands attenuates mitophagy impairments and modulates mitochondrial dynamics in neuroblastoma cells expressing mutant tau and APP. Taken together, these findings suggest that TSPO plays a neuroprotective role in AD pathology and highlights its therapeutic potential as a drug target for AD.
DOI: 10.32657/10356/160865
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Theses

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