Anti-inflammatory potential of thymosin β4 in the central nervous system: implications for progressive neurodegenerative diseases

ABSTRACT

Introduction: The actin-sequestering thymosin beta4 (Tβ4) is the most abundant member of the β-thymosins, and is widely expressed in the central nervous system (CNS), but its functions in the healthy and diseased brain are poorly understood. The expression of Tβ4 in neurons and microglia, the resident immune cells of the brain, suggests that it can play a role in modulating behavioral processes and immunological mechanisms in the brain. The purpose of this review is to shed lights on the role of Tβ4 in CNS function and diseases without antecedent autoimmune inflammation or injury, and to question its therapeutic potential for neurodegenerative disorders such as Alzheimer’s disease.

Areas covered: This review presents the evidence supporting a role for Tβ4 in behaviors that are affected in CNS disorders, as well as studies linking Tβ4 upregulation in microglia to neuroinflammatory processes associated with these disorders. Finally, the implication of Tβ4 in the process of microglial activation and the mechanisms underlying its ability to suppress pro-inflammatory signaling in microglia are discussed.

Expert opinion: Tβ4 has the potential to control inflammatory processes in the brain, opening avenues for new therapeutic applications to a range of neurodegenerative conditions.

KEYWORDS:

• Thymosin β4
• neuroinflammation
• microglia
• central nervous system disorders

Article highlights

• Thymosin β4 (Tβ4) is widely expressed in the central nervous system (CNS), but its role in the healthy and diseased brain remains poorly understood

• Indirect evidence suggest a role for Tβ4 in hippocampus-mediated memory and behaviors known to be altered in cognitive and psychiatric disorders

• Tβ4 is also associated with reactive gliosis in neurodegenerative diseases, where it could play a role in dampening inflammation and promoting repair

• Tβ4 may play a role in microglial activation and de-activation in response to CNS insults and proinflammatory stimuli.

• Tβ4 has proven potential for the treatment of traumatic and neurological brain injuries but could also be a promising therapeutic avenue to reduce neuroinflammation associated with the pathogenesis of progressive psychiatric and neurodegenerative disorders, and to alleviate their symptoms.

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Declaration of interest

The authors have no 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.

Reviewer disclosures

One reviewer has declared that they are listed on a patent on the use of Thymosin beta4 in neurological diseases.

Additional information

Funding

This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.