TSPO Regulation in Reactive Gliotic Diseases
Document Type
Article
Publication Date
1-6-2018
Publication Title
Journal of Neuroscience Research
Volume
96
Issue
6
First page number:
978
Last page number:
988
Abstract
The brain is the most metabolically active organ in the body. This high metabolic demand is apparent in that 60% of the brain is comprised of mitochondria‐enriched cells. A disruption of the brain's ability to meet this immense metabolic demand is central to the pathogenesis of a multitude of neurological disorders, which range from depression to Alzheimer's disease. Central to these pathologies are glial signaling and energy metabolism cascades regulating apoptosis and inflammation. Thus, diseases causing inflammation and disruption of metabolism can be correlated with glial reactivity. Acutely, reactive gliosis provides a mechanism for limiting the progression of a disease. Following chronic activation, the ability of reactive gliosis to limit disease progression decreases and, in some cases, transitions into a harmful state. The necessity for a noninvasive biomarker of disease in the brain has linked reactive gliosis with an upregulation of translocator protein (TSPO). TSPO is an 18kDa protein that is both a therapeutic target for multiple acute and chronic neuroinflammatory diseases and the leading biomarker for Alzheimer's disease. Although a central function of TSPO is not well known, the protein was named for its ability to translocate cholesterol. Increased TSPO expression is an indicator of disrupted metabolic activity and increased reactive oxygen production. The changes in TSPO expression levels both temporally and spatially relate to the pathogenesis of stroke, Alzheimer's disease, traumatic brain injury, and depression. Therefore, research into the basic function and potential therapeutics targeting TSPO will have broad implications for many diseases of the brain.
Disciplines
Molecular and Cellular Neuroscience | Neuroscience and Neurobiology | Psychiatry and Psychology
Language
English
Repository Citation
McNeela, A. M.,
Bernick, C.,
Hines, R. M.,
Hines, D. J.
(2018).
TSPO Regulation in Reactive Gliotic Diseases.
Journal of Neuroscience Research, 96(6),
978-988.
http://dx.doi.org/10.1002/jnr.24212