Identification of causative genes for hereditary spastic paraplegia
Description: We identified that mutations in the UBAP1 gene cause a new type (SPG80) of hereditary spastic paraplegia (HSP) independently with European and American study groups. The full-length UBAP1 protein is involved in endosomal dynamics in neurons, while loss of UBAP1 function may perturb endosomal fusion and sorting of ubiquitinated cargos.These effects could be more prominent in neurons, thereby giving rise to the phenotype of a neurodegenerative disease such as HSP. We established the UBAP1 knock-in mice to elucidate the further molecular mechanism underlying SPG80 and to find the disease-modifying therapy for SPG80. In addition, we found a lot of novel mutations in SPG4, SPG5, SPG9B, SPG11, SPG57, SPG72, PLA2G6, VCP, and AP-4 associated HSP, and performed clinical and genetic studies of these HSP.
Amount: ¥4,420,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2021-03-31
Investigator: Yoshihisa Takiyama
Institution: University of Yamanashi
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 28
Funder award ID: 18K07495
OpenAlex ID: G6784652740