TY - JOUR
T1 - The mitochondrial translocator protein (TSPO) in Alzheimer's disease
T2 - Therapeutic and immunomodulatory functions
AU - Fairley, Lauren H.
AU - Lai, Kei Onn
AU - Grimm, Amandine
AU - Eckert, Anne
AU - Barron, Anna M.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/9
Y1 - 2024/9
N2 - The translocator protein (TSPO) has been widely investigated as a PET-imaging biomarker of neuroinflammation and, more recently, as a therapeutic target for the treatment of neurodegenerative disease. TSPO ligands have been shown to exert neuroprotective effects in vivo and in vitro models of Alzheimer's disease (AD), by reducing toxic beta amyloid peptides, and attenuating brain atrophy. Recent transcriptomic and proteomic analyses, and the generation of TSPO-KO mice, have enabled new insights into the mechanistic function of TSPO in AD. Using a multi-omics approach in both TSPO-KO- and TSPO ligand-treated mice, we have demonstrated a key role for TSPO in microglial respiratory metabolism and phagocytosis in AD. In this review, we discuss emerging evidence for therapeutic and immunomodulatory functions of TSPO in AD, and new tools for studying TSPO in the brain.
AB - The translocator protein (TSPO) has been widely investigated as a PET-imaging biomarker of neuroinflammation and, more recently, as a therapeutic target for the treatment of neurodegenerative disease. TSPO ligands have been shown to exert neuroprotective effects in vivo and in vitro models of Alzheimer's disease (AD), by reducing toxic beta amyloid peptides, and attenuating brain atrophy. Recent transcriptomic and proteomic analyses, and the generation of TSPO-KO mice, have enabled new insights into the mechanistic function of TSPO in AD. Using a multi-omics approach in both TSPO-KO- and TSPO ligand-treated mice, we have demonstrated a key role for TSPO in microglial respiratory metabolism and phagocytosis in AD. In this review, we discuss emerging evidence for therapeutic and immunomodulatory functions of TSPO in AD, and new tools for studying TSPO in the brain.
KW - Alzheimer's disease
KW - Dementia
KW - Inflammation
KW - Mitochondria
KW - Positron emission tomography
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UR - http://www.scopus.com/inward/citedby.url?scp=85198089625&partnerID=8YFLogxK
U2 - 10.1016/j.biochi.2024.07.003
DO - 10.1016/j.biochi.2024.07.003
M3 - Review article
C2 - 38971458
AN - SCOPUS:85198089625
SN - 0300-9084
VL - 224
SP - 120
EP - 131
JO - Biochimie
JF - Biochimie
ER -