Modulation of Heat Shock Response Proteins by ASS234, Targeted for Neurodegenerative Diseases Therapy

Chem Res Toxicol. 2018 Sep 17;31(9):839-842. doi: 10.1021/acs.chemrestox.8b00192. Epub 2018 Aug 27.

Abstract

ASS234 is a new multitarget molecule with multiple neuroprotective actions that significantly elevate mRNA levels of NRF2 and HSF1 transcriptional factors and of HSP105, HSP90AB1, HSPA1A, HSPA1B, HSPA5, HSPA8, HSPA9, HSP60, DNAJA1, DNAJB1, DNAJB6, DNAJC3, DNAJC5, DNAJC6, HSPB1, HSPB2, HSPB5, HSPB6, HSPB8, and HSP10 heat shock proteins (HSPs) family members in SH-SY5Y cells. This NRF2 and HSF1 overexpression may explain the upregulation of both the antioxidant enzymes previously described and the members of the HSPs family observed. These findings suggest that ASS234 is a potent HSPs inductor, which might be beneficial for preventing protein misfolding aggregation and cell death in Alzheimer's disease and other neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Cell Line, Tumor
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins / drug effects*
  • Heat-Shock Proteins / physiology
  • Humans
  • Indoles / pharmacology*
  • Neurodegenerative Diseases / prevention & control*
  • Neuroprotective Agents / pharmacology*
  • Piperidines / pharmacology*
  • Up-Regulation

Substances

  • Antioxidants
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Indoles
  • N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine
  • Neuroprotective Agents
  • Piperidines