Díaz-Martínez Néstor Emmanuel, Velasco Iván
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México.
Rev Invest Clin. 2009 Mar-Apr;61(2):140-9.
Chondroitin sulphate proteoglycans (CSPG) are components of the extracellular matrix, consisting of peptides chemically attached covalently to chains of glycosaminoglycans. There are 4 families of CSPG including lecticans, which are found mainly in the central nervous system (CNS) of vertebrates. In vitro studies have shown a negative effect of these proteoglycans on axonal growth, mediated by depolymerization of actin filaments in the neuronal cytoskeleton. In some neurodegenerative diseases, and especially after traumatic injuries of adult CNS, there are increased levels of CSPG expression. Axonal growth inhibition by CSPG has been observed also in vivo, and therefore a strategy aimed to counteract the inhibition of axonal growth might lead to new therapies designed to restore neural circuits. There is compelling in vivo evidence that CSPG degradation by Chondroitinase ABC allows both axonal growth and functional recovery in models of injury in the mammalian CNS. These data suggest that manipulation of the response to damage could result in effective ways to promote recovery of nerve functions in neurological disorders that affect humans, such as spinal cord lesions or Parkinson disease.
硫酸软骨素蛋白聚糖(CSPG)是细胞外基质的组成成分,由化学共价连接到糖胺聚糖链上的肽组成。CSPG有4个家族,包括凝集素,主要存在于脊椎动物的中枢神经系统(CNS)中。体外研究表明,这些蛋白聚糖通过神经元细胞骨架中肌动蛋白丝的解聚,对轴突生长产生负面影响。在一些神经退行性疾病中,尤其是成人中枢神经系统受到创伤后,CSPG的表达水平会升高。在体内也观察到CSPG对轴突生长的抑制作用,因此,旨在对抗轴突生长抑制的策略可能会带来旨在恢复神经回路的新疗法。有令人信服的体内证据表明,在哺乳动物中枢神经系统损伤模型中,软骨素酶ABC降解CSPG可促进轴突生长和功能恢复。这些数据表明,对损伤反应的调控可能会产生有效的方法,以促进影响人类的神经系统疾病(如脊髓损伤或帕金森病)中神经功能的恢复。