Bone morphogenetic proteins in multiple sclerosis: Role in neuroinflammation

Abstract

Bone morphogenetic proteins (BMPs) are growth factors that represent the largest subgroup of signalling ligands of the transforming growth factor beta (TGF-β) superfamily. Their participation in the proliferation, survival and cell fate of several cell types and their involvement in many pathological conditions are now well known. BMP expression is altered in multiple sclerosis (MS) patients, suggesting that BMPs have a role in the pathogenesis of this disease. MS is a demyelinating and neurodegenerative autoimmune disorder of the central nervous system (CNS). MS is a complex pathological condition in which genetic, epigenetic and environmental factors converge, although its aetiology remains elusive. Multifunctional molecules, such as BMPs, are extremely interesting in the field of MS because they are involved in the regulation of several adult tissues, including the CNS and the immune system. In this review, we discuss the extensive data available regarding the role of BMP signalling in neuronal progenitor/stem cell fate and focus on the participation and expression of BMPs in CNS demyelination. Additionally, we provide an overview of the involvement of BMPs as modulators of the immune system, as this subject has not been thoroughly explored even though it is of great interest in autoimmune disorders. Moreover, we describe the data on BMP signalling in autoimmunity and inflammatory diseases, including MS and its experimental models. Thus, we aim to provide an integrated view of the putative role of BMPs in MS pathogenesis and to open the field for the further development of alternative therapeutic strategies for MS patients.

Keywords: Autoimmunity; Bone morphogenetic proteins; Experimental autoimmune encephalomyelitis; Immune regulation; Multiple sclerosis; Neurodegeneration.