TGF-β/BMPs: Crucial crossroad in neural autoimmune disorders

• Published in: Neurochemistry international 2011-10, Vol.59 (5), p.542-550
• Main Authors: Voumvourakis, Konstantine I., Antonelou, Roubina Ch, Kitsos, Dimitrios K., Stamboulis, Eleftherios, Tsiodras, Sotirios
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Autoimmune Diseases - genetics; Autoimmune Diseases - metabolism; Autoimmune Diseases - physiopathology; Biological and medical sciences; BMPs; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - physiology; Epidermis - growth & development; Fundamental and applied biological sciences. Psychology; Humans; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - physiopathology; Nervous System - embryology; Nervous System - growth & development; Nervous System Diseases - genetics; Nervous System Diseases - metabolism; Nervous System Diseases - physiopathology; SMAD proteins; Smad Proteins - genetics; Smad Proteins - physiology; TGF-β; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2011.06.004

► Smad superfamily play a crucial role in the transduction of TGF-β/BMP signaling pathway. ► Both neural and skin development follow the “biphasic developmental model”. ► Many molecules exhibit a biphasic role in the developmental process. ► Some molecules exhibit an enhancing role in one pathway and an inhibiting in the other. ► TGF-β/BMP molecules play a crucial role in the pathophysiology of multiple sclerosis. Transforming growth factor beta (TGF-β) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-β and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-β and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role in the pathophysiology of this disorder by using references from embryonic experimental research. Available literature in the TGF/BMP signalling cascade, mostly during embryonic development of the nervous system is being reviewed. An attempt is made to further elucidate a potential role of TGF/BMP signalling in the pathophysiology of MS. During demyelination, BMP signaling, through various molecular mechanisms, directs the development of the adult neural stem cell in the astrocyte rather than the oligodendrocyte direction, therefore inhibiting the repair process. Further understanding of the above relationships could lead to the development of potentially efficient therapies for MS in the future.