The role of TGF-β superfamily signaling in neurological disorders.

Risa Kashima,Akiko Hata

doi:10.1093/abbs/gmx124

Abstract

The TGF-β superfamily signaling is involved in a variety of biological processes during embryogenesis and in adult tissue homeostasis. Faulty regulation of the signaling pathway that transduces the TGF-β superfamily signals accordingly leads to a number of ailments, such as cancer and cardiovascular, metabolic, urinary, intestinal, skeletal, and immune diseases. In recent years, a number of studies have elucidated the essential roles of TGF-βs and BMPs during neuronal development in the maintenance of appropriate innervation and neuronal activity. The new advancement implicates significant roles of the aberrant TGF-β superfamily signaling in the pathogenesis of neurological disorders. In this review, we compile a number of reports implicating the deregulation of TGF-β/BMP signaling pathways in the pathogenesis of cognitive and neurodegenerative disorders in animal models and patients. We apologize in advance that the review falls short of providing details of the role of TGF-β/BMP signaling or mechanisms underlying the pathogenesis of neurological disorders. The goal of this article is to reveal a gap in our knowledge regarding the association between TGF-β/BMP signaling pathways and neuronal tissue homeostasis and development and facilitate the research with a potential to develop new therapies for neurological ailments by modulating the pathways.

Highlights

The transforming growth factor-β (TGF-β) superfamily of growth factors comprises approximately 20 evolutionarily conserved cytokines subdivided into several families, including TGF-βs, bone morphogenetic proteins (BMPs), activins, inhibins, nodals, and growth and differentiation factors (GDFs) (Table 1) [1]
In the Ema mutant, Tkv, phospho-Mad, and synaptic bouton number are all increased, but they can all be reversed by overexpression of human CLEC16A [112]. These results suggest that Ema and CLE16A inhibit BMP signaling through endolysosomal trafficking and degradation of the signaling components [112]
We summarized studies describing the association of deregulation of TGF-β signaling with neuronal development and neurological disorders

Summary

Introduction

The transforming growth factor-β (TGF-β) superfamily of growth factors comprises approximately 20 evolutionarily conserved cytokines subdivided into several families, including TGF-βs, bone morphogenetic proteins (BMPs), activins, inhibins, nodals, and growth and differentiation factors (GDFs) (Table 1) [1]. They bind to two sets of ligand-specific receptors (Types I and II), which contain serine/threonine kinases. It is known that the TGF-β/BMP signal can be transduced through a variety of intracellular Smad-independent pathways, including LIM domain kinase 1 (LIMK1)-actin depolymerizing factor (ADF)-cofilin and mitogen activated protein kinase pathways (known as ‘noncanonical’) [4] (Fig. 1). We try to discuss the roles of TGF-β signaling pathways in neuronal diseases and to reveal a gap in our knowledge regarding the association between TGF-β/ BMP signaling pathways and neuronal tissue homeostasis and development

Objectives

Findings

Conclusion