RESUMO
This review focuses on the influence of laminins, mediated through laminin receptors present on Schwann cells, on peripheral nerve development and pathology. Laminins influence multiple aspects of cell differentiation and tissue morphogenesis, including cell survival, proliferation, cytoskeletal rearrangements, and polarity. Peripheral nerves are no exception, as shown by the discovery that defective laminin signals contribute to the pathogenesis of diverse neuropathies such as merosin-deficient congenital muscular dystrophy and Charcot-Marie-Tooth 4F, neurofibromatosis, and leprosy. In the last 5 years, advanced molecular and cell biological techniques and conditional mutagenesis in mice began revealing the role of different laminins and receptors in developing nerves. In this way, we are starting to explain morphological and pathological observations beginning at the start of the last century. Here, we review these recent advances and show how the roles of laminins and their receptors are surprisingly varied in both time and place.
Assuntos
Laminina/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Receptores de Laminina/metabolismo , Células de Schwann/metabolismo , Animais , Humanos , Laminina/classificação , Hanseníase/metabolismo , Hanseníase/patologia , Modelos Biológicos , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/ultraestrutura , Doenças do Sistema Nervoso Periférico/patologia , Receptores de Laminina/classificaçãoRESUMO
Demyelination results in severe disability in many neurodegenerative diseases and nervous system infections, and it is typically mediated by inflammatory responses. Mycobacterium leprae, the causative organism of leprosy, induced rapid demyelination by a contact-dependent mechanism in the absence of immune cells in an in vitro nerve tissue culture model and in Rag1-knockout (Rag1-/-) mice, which lack mature B and T lymphocytes. Myelinated Schwann cells were resistant to M. leprae invasion but undergo demyelination upon bacterial attachment, whereas nonmyelinated Schwann cells harbor intracellular M. leprae in large numbers. During M. leprae-induced demyelination, Schwann cells proliferate significantly both in vitro and in vivo and generate a more nonmyelinated phenotype, thereby securing the intracellular niche for M. leprae.