1. TECPR2: a new autophagy link for neurodegeneration.
- Author
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Oz-Levi D, Gelman A, Elazar Z, and Lancet D
- Subjects
- HeLa Cells, Humans, Mitochondria metabolism, Mutation genetics, Nerve Tissue Proteins genetics, Paraparesis, Spastic genetics, Paraparesis, Spastic pathology, Proteolysis, Signal Transduction, Autophagy, Nerve Tissue Proteins metabolism, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology
- 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.
- Published
- 2013
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