tailieunhanh - Báo cáo khoa học: Molecular mechanisms in successful peripheral regeneration

Peripheral nerve injury is normally followed by a robust regenerative response. Here we describe the early changes associated with injury from the initial rise in intracellular calcium and the subsequent activation of transcription factors and cytokines leading to an inflammatory reaction, and the expression of growth factors, cytokines, neuropeptides, and other secreted molecules involved in cell-to-cell communication promoting regen-eration and neurite outgrowth. | iFEBS Journal REVIEW ARTICLE Molecular mechanisms in successful peripheral regeneration Milan Makwana1 and Gennadij Raivich1 2 1 Centre for PerinatalBrain Protection Repair Department of Obstetrics and Gynaecology University College London UK 2 Department of Anatomy University College London UK Keywords adhesion molecule axonalgrowth cone cell survival cytokine cytoskeleton mitogen-activated protein kinase nerve regeneration neurotrophin reinnervation transcription factor Correspondence G. Raivich Centre for Perinatal Brain Protection Repair Department of Obstetrics Gynaecology Department of Anatomy University College London 86-96 Chenies Mews London WC1E 6HX UK Fax 44 207 383 7429 Tel 44 207 679 6068 E-mail Received 7 February 2005 accepted 4 April 2005 doi Peripheral nerve injury is normally followed by a robust regenerative response. Here we describe the early changes associated with injury from the initial rise in intracellular calcium and the subsequent activation of transcription factors and cytokines leading to an inflammatory reaction and the expression of growth factors cytokines neuropeptides and other secreted molecules involved in cell-to-cell communication promoting regeneration and neurite outgrowth. The aim of this review is to summarize the molecular mechanisms that play a part in executing successful regeneration. Injury to neurons results in a sequence of molecular and cellular responses that are associated with and that may play an important role in the mounting of a successful regenerative response and the ensuing recovery of function. In the injured neuron the rapid arrival of signals that contribute to cellular injury and stress is followed by the induction of transcription factors adhesion molecules growth-associated proteins and structural components needed for axonal elongation. These changes are accompanied by immense shifts in cellular organization the appearance of growth cones at the