ABSTRACT
Hereditary spastic paraplegia (HSP) is a group of significantly clinically and genetically heterogeneous neurodegenerative disorders, which are predominantly characterized by progressive lower limbs weakness and spasticity, and spastic paraplegia type 4 (SPG4) is the most common type among them. So far, mutations in 78 distinct loci and 59 mutated genes have been identified in patients with HSP. The protein spastin coded by the SPAST gene plays a critical role in regulating length, number and activity of microtubules, as well as the occurrence and development of various organelles. It is generally believed that the mutated spastin leads to partial or total loss of the function, which is the main pathogenetic mechanism. While recent studies have also suggested that there may exist acquired neurotoxic effects of mutant proteins by the two isoforms (M1, M87) coded by the SPAST gene, which is also one of the critical mechanisms. In this paper, the pathogenesis of SPG4 was reviewed.
ABSTRACT
Hereditary spastic paraplegia (HSP) is a group of significantly clinically and genetically heterogeneous neurodegenerative disorders, which are predominantly characterized by progressive lower limbs weakness and spasticity, and spastic paraplegia type 4 (SPG4) is the most common type among them. So far, mutations in 78 distinct loci and 59 mutated genes have been identified in patients with HSP. The protein spastin coded by the SPAST gene plays a critical role in regulating length, number and activity of microtubules, as well as the occurrence and development of various organelles. It is generally believed that the mutated spastin leads to partial or total loss of the function, which is the main pathogenetic mechanism. While recent studies have also suggested that there may exist acquired neurotoxic effects of mutant proteins by the two isoforms (M1, M87) coded by the SPAST gene, which is also one of the critical mechanisms. In this paper, the pathogenesis of SPG4 was reviewed.