Moloughney Joseph G, Weisleder Noah
Department of Neuroscience and Cell Biology, UMDNJ- Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Recent Pat Biotechnol. 2012 Dec;6(3):200-11. doi: 10.2174/1872208311206030200.
Maintenance of the integrity of the plasma membrane is essential for maintenance of cellular function and prevention of cell death. Since the plasma membrane is frequently exposed to a variety of mechanical and chemical insults the cell has evolved active processes to defend against these injuries by resealing disruptions in the plasma membrane. Cell membrane repair is a conserved process observed in nearly every cell type where intracellular vesicles are recruited to sites of membrane disruption where they can fuse with themselves or the plasma membrane to create a repair patch. When disruptions are extensive or there is an underlying pathology that reduces the membrane repair capacity of a cell this defense mechanism may prove insufficient and the cell could die due to breakdown of the plasma membrane. Extensive loss of cells can compromise the integrity and function of tissues and leading to disease. Thus, methods to increase membrane resealing capacity could have broad utility in a number of disease states. Efforts to find reagents that can modulate plasma membrane reseal found that specific tri-block copolymers, such as poloxamer 188 (P188, or Pluronic F68), can increase the structural stability and resealing of the plasma membrane. Here we review several current patents and patent applications that present inventions making use of P188 and other copolymers to treat specific disease states such as muscular dystrophy, heart failure, neurodegenerative disorders and electrical injuries, or to facilitate biomedical applications such as transplantation. There appears to be promise for the application of poloxamers in the treatment of various diseases, however there are potential concerns with toxicity with long term application and bioavailability in some cases.
维持质膜的完整性对于维持细胞功能和防止细胞死亡至关重要。由于质膜经常受到各种机械和化学损伤,细胞已经进化出主动过程,通过重新封闭质膜中的破坏来抵御这些损伤。细胞膜修复是一个在几乎每种细胞类型中都能观察到的保守过程,其中细胞内囊泡被招募到膜破坏部位,在那里它们可以与自身或质膜融合以形成修复补丁。当破坏广泛或存在潜在病理状况导致细胞的膜修复能力降低时,这种防御机制可能被证明是不足的,细胞可能因质膜破裂而死亡。大量细胞损失会损害组织的完整性和功能并导致疾病。因此,提高膜重新封闭能力的方法在许多疾病状态中可能具有广泛的用途。寻找能够调节质膜重新封闭的试剂的努力发现,特定的三嵌段共聚物,如泊洛沙姆188(P188,或普朗尼克F68),可以增加质膜的结构稳定性和重新封闭能力。在这里,我们回顾了几项当前的专利和专利申请,这些发明利用P188和其他共聚物来治疗特定的疾病状态,如肌肉萎缩症、心力衰竭、神经退行性疾病和电击伤,或促进生物医学应用,如移植。泊洛沙姆在各种疾病治疗中的应用似乎有前景,然而,长期应用存在潜在的毒性问题,在某些情况下还存在生物利用度问题。