Salinas Sara, Carazo-Salas Rafael E, Proukakis Christos, Schiavo Giampietro, Warner Thomas T
Molecular NeuroPathobiology, Cancer Research United Kingdom London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
J Neurosci Res. 2007 Sep;85(12):2778-82. doi: 10.1002/jnr.21238.
SPG4, the gene encoding for spastin, a member of the ATPases associated with various cellular activities (AAA) family, is mutated in around 40% of cases of autosomal dominant hereditary spastic paraplegia (AD-HSP). This group of neurodegenerative diseases is characterized by a progressive spasticity and lower limb weakness with degeneration of terminal axons in cortico-spinal tracts and dorsal columns. Spastin has two main domains, a microtubule interacting and endosomal trafficking (MIT) domain at the N-terminus and the C-terminus AAA domain. Early studies suggested that spastin interacts with microtubules similarly to katanin, a member of the same subgroup of AAA. Recent evidence confirmed that spastin possesses microtubule-severing activity but can also bundle microtubules in vitro. Understanding the physiologic and pathologic involvement of these activities and their regulation is critical in the study of HSP.
SPG4基因编码与多种细胞活动相关的ATP酶（AAA）家族成员痉挛素，在约40%的常染色体显性遗传性痉挛性截瘫（AD - HSP）病例中发生突变。这类神经退行性疾病的特征是进行性痉挛和下肢无力，伴随皮质脊髓束和背柱中终末轴突的退化。痉挛素具有两个主要结构域，N端的微管相互作用及内体运输（MIT）结构域和C端的AAA结构域。早期研究表明，痉挛素与微管的相互作用类似于AAA同亚组的成员katanin。最近的证据证实，痉挛素具有微管切断活性，但在体外也能使微管成束。了解这些活动的生理和病理参与情况及其调节，对遗传性痉挛性截瘫的研究至关重要。
