Pathogenic mechanisms and therapeutic approaches for HSP caused by mutations in SPG7

Subproject 8

Project lead: Elena Rugarli (Universität Köln)


Mutations in SPG7 are among the most common causes of recessive and sporadic cases of hereditary spastic paraplegia (HSP). SPG7 encodes paraplegin, a mitochondrial protease involved in the quality control of inner membrane mitochondrial proteins and the maturation of specific substrates. In the absence of paraplegin, mitochondria show abnormal Ca2+ uptake and swelling. 
In this project, we want to use a previously developed Spg7 knock-out mouse model that recapitulates the main characteristics of human disease to expand our knowledge of the mechanisms leading to HSP and to develop new therapeutic approaches. 
Our goals are 1) to discover common pathogenic mechanisms between SPG7-HSP and other non-mitochondrial forms of HSP or Wallerian degeneration; 2) to explore the benefits of treatment in SPG7-HSP targeting astrocyte function.