design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis设计和筛选胶质特异性的细胞穿透肽在多发性硬化症治疗应用.pdfVIP

Design and Screening of a Glial Cell-Specific, Cell Penetrating Peptide for Therapeutic Applications in Multiple Sclerosis 1 1 3 2 1,4 Corey Heffernan , Huseyin Sumer , Gilles J. Guillemin , Ursula Manuelpillai , Paul J. Verma * 1 Reprogramming and Stem Cell Laboratory, Centre for Reproduction Development, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia, 2 Placental Stem Cell Laboratory, Centre for Reproduction Development, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia, 3 Department of Pharmacology, University of New South Wales, Sydney, New South Wales, Australia, 4 South Australian Research and Development Industry, Turretfield Research Centre, Rosedale, South Australia, Australia Abstract Multiple Sclerosis (MS) is an autoimmune, neurodegenerative disease of the central nervous system (CNS) characterized by demyelination through glial cell loss. Current and proposed therapeutic strategies to arrest demyelination and/or promote further remyelination include: (i) modulation of the host immune system; and/or (ii) transplantation of myelinating/stem or progenitor cells to the circulation or sites of injury. However, significant drawbacks are inherent with both approaches. Cell penetrating peptides (CPP) are short amino acid sequences with an intrinsic ability to translocate across plasma membranes, and theoretically represent an attractive vector for delivery of therapeutic peptides or nanoparticles to glia to promote cell survival or remyelination. The CPPs described to date are commonly non-selective in the cell types they transduce, limiting their therapeutic application in vivo. Here, we describe a theoretical