thymosin-beta(4) and Neurodegenerative-Diseases

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.

Topics: Humans; Inflammation; Interleukin-1; Interleukin-1 Receptor-Associated Kinases; MicroRNAs; Neurodegenerative Diseases; NF-kappa B; Signal Transduction; Thymosin; Toll-Like Receptors

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

Topics: Animals; Anti-Inflammatory Agents; Central Nervous System; Disease Progression; Humans; Inflammation; Neurodegenerative Diseases; Signal Transduction; Thymosin

Thymosin β4 (Tβ4) promotes CNS and peripheral nervous system (PNS) plasticity and neurovascular remodeling leading to neurological recovery in a range of neurological diseases. Treatment of neural injury and neurodegenerative disease 24 h or more post-injury and disease onset with Tβ4 enhances angiogenesis, neurogenesis, neurite and axonal outgrowth, and oligodendrogenesis, and thereby, significantly improves functional and behavioral outcomes. We propose that oligodendrogenesis is a common link by which Tβ4 promotes recovery after neural injury and neurodegenerative disease. The ability to target many diverse restorative processes via multiple molecular pathways that drive oligodendrogenesis and neurovascular remodeling may be mediated by the ability of Tβ4 to alter cellular expression of microRNAs (miRNAs). However, further investigations on the essential role of miRNAs in regulating protein expression and the remarkable exosomal intercellular communication network via exosomes will likely provide insight into mechanisms of action and means to amplify the therapeutic effects of Tβ4.

Topics: Animals; Cell Communication; Humans; Neurodegenerative Diseases; Neurogenesis; Thymosin