International journal of molecular sciences, 2020-07, Vol.21 (15), p.5442
2020
Details
- Autor(en) / Beteiligte
- Titel
- Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels
- Ist Teil von
- International journal of molecular sciences, 2020-07, Vol.21 (15), p.5442
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Misfolding, aggregation and accumulation of proteins are toxic elements in the progression of a broad range of neurodegenerative diseases. Molecular chaperones enable a cellular defense by reducing or compartmentalizing these insults. Small heat shock proteins (sHsps) engage proteins early in the process of misfolding and can facilitate their proper folding or refolding, sequestration, or clearance. Here, we evaluate the effects of the sHsp Hsp22, as well as a pseudophosphorylated mutant and an N-terminal domain deletion (NTDΔ) variant on tau aggregation in vitro and tau accumulation and aggregation in cultured cells. Hsp22 wild-type (WT) protein had a significant inhibitory effect on heparin-induced aggregation in vitro and the pseudophosphorylated mutant Hsp22 demonstrated a similar effect. When co-expressed in a cell culture model with tau, these Hsp22 constructs significantly reduced soluble tau protein levels when transfected at a high ratio relative to tau. However, the Hsp22 NTDΔ protein drastically reduced the soluble protein expression levels of both tau WT and tau P301L/S320F even at lower transfection ratios, which resulted in a correlative reduction of the triton-insoluble tau P301L/S320F aggregates.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms21155442Titel-ID: cdi_doaj_primary_oai_doaj_org_article_51184ddcd7b0414e803ab2c509eb21a3
- Format
- –
- Schlagworte
- Accumulation, Alzheimer’s disease, Animals, Binding sites, Cell culture, Chaperones, Disease, Domains, Gene Expression Regulation - genetics, Heat shock proteins, Heat-Shock Proteins - genetics, Heat-Shock Proteins, Small - genetics, Heparin, Humans, Kinases, Mice, Mice, Transgenic, molecular chaperones, Molecular Chaperones - genetics, Mutants, Mutation, neurodegeneration, Neurodegenerative Diseases - genetics, Neurodegenerative Diseases - pathology, Phosphorylation, Protein Aggregation, Pathological - genetics, Protein Binding - genetics, Protein folding, Proteostasis Deficiencies - genetics, small heat shock protein 22, Small heat shock proteins, tau, Tau protein, tau Proteins - genetics, Transfection