A new insight into thymosin β4, a promising therapeutic approach for neurodegenerative disorders

J Cell Physiol. 2020 Apr;235(4):3270-3279. doi: 10.1002/jcp.29293. Epub 2019 Oct 14.

Abstract

Thymosin β4 (Tβ4), a G-actin-sequestering secreted peptide, improves neurovascular remodeling and central nervous system plasticity, which leads to neurological recovery in many neurological diseases. Inflammatory response adjustment and tissue inflammation consequences from neurological injury are vital for neurological recovery. The innate or nonspecific immune system is made of different components. The Toll-like receptor pro-inflammatory signaling pathway, which is one of these components, regulates tissue injury. The main component of the Toll-like/IL-1 receptor signaling pathway, which is known as IRAK1, can be regulated by miR-146a and regulates NF-κB expression. Due to the significant role of Tβ4 in oligodendrocytes, neurons, and microglial cells in neurological recovery, it is suggested that Tβ4 regulates the Toll-like receptor (TLR) pro-inflammatory signaling pathway by upregulating miR-146a in neurological disorders. However, further investigations on the role of Tβ4 in regulating the expression of miR146a and TLR signaling pathway in the immune response adjustment in neurological disorders provides an insight into mechanisms of action and the possibility of Tβ4 therapeutic effect enhancement.

Keywords: CNS; TLR; Tβ4; diseases; miR-146a; neurodegenerative disorder.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Inflammation / genetics*
  • Inflammation / pathology
  • Interleukin-1 / genetics
  • Interleukin-1 Receptor-Associated Kinases / genetics*
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / pathology
  • Signal Transduction / genetics
  • Thymosin / genetics*
  • Toll-Like Receptors / genetics

Substances

  • Interleukin-1
  • MIRN146 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Toll-Like Receptors
  • thymosin beta(4)
  • Thymosin
  • IRAK1 protein, human
  • Interleukin-1 Receptor-Associated Kinases