TY - JOUR
T1 - A protective role of translocator protein in Alzheimer’s disease brain
AU - Jung, Marianna E.
N1 - Funding Information:
This work was supported by the National Institutes of Health/National Institutes on Aging grant number (AG053974).
Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - Translocator Protein (18 kDa) (TSPO) is a mitochondrial protein that locates cytosol cholesterol to mitochondrial membranes to begin the synthesis of steroids including neurotrophic neuroster-oids. TSPO is abundantly present in glial cells that support neurons and respond to neuroinflammation. Located at the outer membrane of mitochondria, TSPO regulates the opening of mitochondrial permeability transition pore (mPTP) that controls the entry of molecules necessary for mitochondrial function. TSPO is linked to neurodegenerative Alzheimer’s Disease (AD) such that TSPO is upregulated in the brain of AD patients and signals AD-induced adverse changes in brain. The initial increase in TSPO in response to brain insults remains elevated to repair cellular damages and perhaps to prevent further neuronal degeneration as AD progresses. To exert such protective activities, TSPO increases the synthesis of neuroprotective steroids, decreases neuroinflammation, limits the opening of mPTP, and reduces the generation of reactive oxygen species. The beneficial effects of TSPO on AD brain are manifested as the attenuation of neurotoxic amyloid β and mitochondrial dysfunction accompanied by the improvement of memory and cognition. However, the protective activities of TSPO appear to be temporary and even-tually diminish as the severity of AD becomes profound. Timely treatment with TSPO agonists/ligands before the loss of endogenous TSPO’s activity may promote the protective functions and may extend neuronal survival.
AB - Translocator Protein (18 kDa) (TSPO) is a mitochondrial protein that locates cytosol cholesterol to mitochondrial membranes to begin the synthesis of steroids including neurotrophic neuroster-oids. TSPO is abundantly present in glial cells that support neurons and respond to neuroinflammation. Located at the outer membrane of mitochondria, TSPO regulates the opening of mitochondrial permeability transition pore (mPTP) that controls the entry of molecules necessary for mitochondrial function. TSPO is linked to neurodegenerative Alzheimer’s Disease (AD) such that TSPO is upregulated in the brain of AD patients and signals AD-induced adverse changes in brain. The initial increase in TSPO in response to brain insults remains elevated to repair cellular damages and perhaps to prevent further neuronal degeneration as AD progresses. To exert such protective activities, TSPO increases the synthesis of neuroprotective steroids, decreases neuroinflammation, limits the opening of mPTP, and reduces the generation of reactive oxygen species. The beneficial effects of TSPO on AD brain are manifested as the attenuation of neurotoxic amyloid β and mitochondrial dysfunction accompanied by the improvement of memory and cognition. However, the protective activities of TSPO appear to be temporary and even-tually diminish as the severity of AD becomes profound. Timely treatment with TSPO agonists/ligands before the loss of endogenous TSPO’s activity may promote the protective functions and may extend neuronal survival.
KW - Alzheimer’s disease (AD)
KW - Amyloid β
KW - Mitochondrial permeability transition pores
KW - Neurosteroids
KW - Reactive oxygen species
KW - Translocator protein (18 kDa)
UR - http://www.scopus.com/inward/record.url?scp=85082390843&partnerID=8YFLogxK
U2 - 10.2174/1567205017666200217105950
DO - 10.2174/1567205017666200217105950
M3 - Review article
C2 - 32065102
AN - SCOPUS:85082390843
SN - 1567-2050
VL - 17
SP - 3
EP - 15
JO - Current Alzheimer Research
JF - Current Alzheimer Research
IS - 1
ER -