Title:Translocator Protein (TSPO) Role in Aging and Alzheimer’s Disease
Volume: 7
Issue: 3
Author(s): Jayanthi Repalli
Affiliation:
Keywords:
Aging, Alzheimer’s disease, apoptosis, mitochondria, neurodegenerative diseases, TSPO.
Abstract: Cellular damage and deregulated apoptotic cell death lead to functional impairment, and a main
consequence of these events is aging. Cellular damage is initiated by different stress/risk factors such as
oxidative stress, inflammation, and heavy metals. These stress/risk factors affect the cellular homeostasis
by altering methylation status of several aging and Alzheimer’s disease associated genes; these effects can
be manifested immediately after exposure to stress and at later stages of life. However, when cellular damage
exceeds certain threshold levels apoptosis is initiated. This review discusses the stress factors involved
in cellular damage and the role and potential of TSPO-mediated cell death in aging as well as in Alzheimer’s disease,
which is also characterized by extensive cell death. Mitochondrial-mediated apoptotic death through the release of cytochrome
c is regulated by TSPO, and increased expression of this protein is observed in both elderly people and in patients
with Alzheimer’s disease. TSPO forms and mediates opening of the mitochondrial membrane pore, mPTP and oxidizes
cardiolipin, and these events lead to the leakage of apoptotic death mediators, such as cytochrome c, resulting in cell
death. However, TSPO has many proposed functions and can also increase steroid synthesis, which leads to inhibition of
inflammation and inhibition of the release of apoptotic factors, thereby decreasing cell damage and promoting cell survival.
Thus, TSPO mediates apoptosis and decreases the cell damage, which in turn dictates the process of aging as well
as the functionality of organs such as the brain. TSPO modulation with ligands in the Alzheimer’s disease mouse model
showed improvement in behavioral symptoms, and studies in Drosophila species showed increased cell survival and prolonged
lifespan in flies after TSPO inhibition. These data suggest that since effects/signs of stress can manifest at any
time, prevention through change in lifestyle and TSPO modulation could be potential strategies for altering both the aging
process and the progression of Alzheimer’s disease.
