The translocator protein as a drug target in Alzheimer’s disease

Abstract

The translocator protein (TSPO) recently emerged as a potential drug target in Alzheimer’s disease (AD). This has been fuelled mainly by positron emission topography studies that show the upregulation of TSPO in AD, especially in relation to microgliosis and astrogliosis in amyloid-β and tau pathology. Although data as to the exact role of TSPO in AD is still inconclusive, TSPO appears to be involved in neuroinflammatory processes and AD has been shown to involve substantial inflammation. Therefore, further development and investigation of the pharmacological effect of TSPO ligands in AD pathology are warranted.

Keywords::

• Alzheimer’s disease
• drug development
• microglia
• neuroinflammation
• positron emission topography
• translocator protein
• TSPO

Financial & competing interests disclosure

The authors receive support from the Australian Research Council and the National Health and Medical Research Council (NHMRC). LM Ittner is a NHMRC Senior Research Fellow. M Kassiou holds patents on all DPA compounds. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Translocator protein (TSPO) is upregulated and possibly functionally involved in neuroinflammation.

• TSPO may form functional homodimers (or functional oligomers).

• TSPO is involved in transmembrane transport of cholesterol, but other functions remains poorly understood.

• TSPO ligands mediate antitumor, anxiolytic and neuroprotective effects in cells and animal models.

• TSPO radioligands may assist in PET imaging for diagnosing Alzheimer’s disease (AD).

• Targeting TSPO improved deficits in a mouse model of AD.

• Further evidence is required to prove that TSPO is a drug target in AD.