Commentary: ZFYVE26/SPASTIZIN: A close link between complicated hereditary spastic paraparesis and autophagy |
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Authors: | Chiara Vantaggiato Emilio Clementi Maria Teresa Bassi |
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Institution: | 1.Scientific Institute IRCCS E. Medea; Laboratory of Molecular Biology; Lecco, Italy;2.Unit of Clinical Pharmacology; Department of Biomedical and Clinical Sciences; University Hospital “Luigi Sacco”; Università di Milano; Milan, Italy |
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Abstract: | Defective autophagy is associated with neurodegenerative disorders including Alzheimer, Parkinson and Huntington diseases, amyotrophic lateral sclerosis and SCA (spinocerebellar ataxias). Autophagy defects were detected also in SPG49, a complicated form of hereditary spastic paraparesis (cHSP) associated with mutations in the TECPR2 gene, suggesting a role of autophagy also in this heterogeneous group of neurodegenerative diseases. We recently found defective autophagy in SPG15, another HSP subtype associated with mutations in the ZFYVE26/SPG15 gene. Patient-derived cells (fibroblasts/lymphoblasts) carrying different ZFYVE26 mutations show accumulation of immature autophagosomes and increased MAP1LC3B-II and SQSTM1/p62 levels. These findings indicate that ZFYVE26 is a key determinant of autophagosome maturation, which is impaired when the protein is defective or absent. Replication of these findings in primary neurons supports the relevance of defective autophagy in SPG15-related neurodegeneration. |
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Keywords: | complicated hereditary spastic paraparesis SPG15 autophagy autophagosome maturation ZFYVE26/SPASTIZIN BECN1/Beclin 1 |
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