title: TECPR2: a new autophagy link for neurodegeneration.
abstract: Autophagy dysfunction has been implicated in a group of progressive neurodegenerative diseases, and has been reported to play a major role in the pathogenesis of these disorders. We have recently reported a recessive mutation in TECPR2, an autophagy-implicated WD repeat-containing protein, in five individuals with a novel form of monogenic hereditary spastic paraparesis (HSP). We found that diseased skin fibroblasts had a decreased accumulation of the autophagy-initiation protein MAP1LC3B/LC3B, and an attenuated delivery of both LC3B and the cargo-recruiting protein SQSTM1/p62 to the lysosome where they are subject to degradation. The discovered TECPR2 mutation reveals for the first time a role for aberrant autophagy in a major class of Mendelian neurodegenerative diseases, and suggests mechanisms by which impaired autophagy may impinge on a broader scope of neurodegeneration.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. ozdanit@gmail.com
authors: Danit
authors: D
authors: Oz-Levi
authors: Amir
authors: A
authors: Gelman
authors: Zvulun
authors: Z
authors: Elazar
authors: Doron
authors: D
authors: Lancet
mesh_terms: D001343:Autophagy; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D020336:Paraparesis, Spastic / Q000235:genetics / Q000473:pathology; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D009419:Nerve Tissue Proteins
keywords: MAP1LC3; autophagy; endosomal trafficking; exome sequencing; hereditary spastic paraparesis; skin fibroblasts