Hsp22 with an N-Terminal Domain Truncation Mediates a Reduction in Tau Protein Levels.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Heat-Shock Proteins/*genetics ; Molecular Chaperones/*genetics ; Neurodegenerative Diseases/*genetics ; tau Proteins/*genetics; Gene Expression Regulation/genetics ; Heat-Shock Proteins, Small/genetics ; Neurodegenerative Diseases/pathology ; Protein Aggregation, Pathological/genetics ; Protein Binding/genetics ; Proteostasis Deficiencies/genetics ; Animals ; Humans ; Mice ; Mice, Transgenic

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.

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RF1AG055088 United States AG NIA NIH HHS; IKBX004214 Department of Veterans' Affairs, Australian Government; I01 BX001637 United States BX BLRD VA; P50 AG016573 United States AG NIA NIH HHS; P50 AG16573 United States AG NIA NIH HHS; RF1 AG055088 United States AG NIA NIH HHS; IK6 BX004214 United States BX BLRD VA; 2I01 BX001637 Department of Veterans' Affairs, Australian Government

Keywords: Alzheimer’s disease; molecular chaperones; neurodegeneration; small heat shock protein 22; tau

0 (HSPB8 protein, human)
0 (Heat-Shock Proteins)
0 (Heat-Shock Proteins, Small)
0 (MAPT protein, human)
0 (Molecular Chaperones)
0 (tau Proteins)

Date Created: 20200806 Date Completed: 20210216 Latest Revision: 20240801

20260130

PMC7432035

10.3390/ijms21155442

32751642