Title:A Protective Role of Translocator Protein in Alzheimer’s Disease Brain
Volume: 17
Issue: 1
关键词:
阿尔茨海默氏病（AD），β淀粉样蛋白，神经类固醇，线粒体通透性过渡孔，活性氧，转运蛋白（18 kDa）。
摘要: Translocator Protein (18 kDa) (TSPO) is a mitochondrial protein that locates cytosol cholesterol
to mitochondrial membranes to begin the synthesis of steroids including neurotrophic neurosteroids.
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 eventually
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.
