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.
ZFYVE26/SPASTIZIN : a close link between complicated hereditary spastic paraparesis and autophagy / C. Vantaggiato, E. Clementi, M.T. Bassi. - In: AUTOPHAGY. - ISSN 1554-8627. - 10:2(2014 Feb), pp. 374-375.
|Titolo:||ZFYVE26/SPASTIZIN : a close link between complicated hereditary spastic paraparesis and autophagy|
CLEMENTI, EMILIO GIUSEPPE IGNAZIO (Secondo)
BASSI, MARIA TERESA (Ultimo)
|Parole Chiave:||BECN1/Beclin 1; SPG15; ZFYVE26/SPASTIZIN; autophagosome maturation; autophagy; complicated hereditary spastic paraparesis; Adaptor Proteins, Signal Transducing; Autophagy; Brain; Carrier Proteins; Humans; Mutation; Neurodegenerative Diseases; Paraparesis, Spastic; Phagosomes|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||feb-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.4161/auto.27173|
|Appare nelle tipologie:||01 - Articolo su periodico|