A protective role of translocator protein in Alzheimer’s disease brain

Marianna E. Jung

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3-15
Number of pages13
JournalCurrent Alzheimer Research
Volume17
Issue number1
DOIs
StatePublished - 1 Jan 2020

Keywords

  • Alzheimer’s disease (AD)
  • Amyloid β
  • Mitochondrial permeability transition pores
  • Neurosteroids
  • Reactive oxygen species
  • Translocator protein (18 kDa)

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