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Cell Stress and Chaperones

, Volume 21, Issue 5, pp 745–753 | Cite as

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation

  • Philip L. HooperEmail author
  • Heather D. Durham
  • Zsolt Török
  • Paul L. Hooper
  • Tim Crul
  • László Vígh
Perspective and Reflection Article

Abstract

Networks of neuronal synapses are the fundamental basis for making and retaining memory. Reduced synapse number and quality correlates with loss of memory in dementia. Heat shock factor 1 (HSF1), the major transcription factor regulating expression of heat shock genes, plays a central role in proteostasis, in establishing and sustaining synaptic fidelity and function, and in memory consolidation. Support for this thesis is based on these observations: (1) heat shock induces improvements in synapse integrity and memory consolidation; (2) synaptic depolarization activates HSF1; (3) activation of HSF1 alone (independent of the canonical heat shock response) augments formation of essential synaptic elements—neuroligands, vesicle transport, synaptic scaffolding proteins, lipid rafts, synaptic spines, and axodendritic synapses; (4) HSF1 coalesces and activates memory receptors in the post-synaptic dendritic spine; (5) huntingtin or α-synuclein accumulation lowers HSF1 while HSF1 lowers huntingtin and α-synuclein aggregation—a potential vicious cycle; and (6) HSF1 agonists (including physical activity) can improve cognitive function in dementia models. Thus, via direct gene expression of synaptic elements, production of HSPs that assure high protein fidelity, and activation of other neuroprotective signaling pathways, HSF1 agonists could provide breakthrough therapy for dementia-associated disease.

Keywords

HSF1 Heat shock factor 1 Memory Synapse, heat shock Heat shock proteins Synapse Synapsin, PSD95 Synaptophysin SAP97 Celastrol B12 Exercise Hyperthermia Fear Emotion Stress Dementia Alzheimer’s Neurodegenerative disease TRP Ethanol Resveratrol SIRT1 GSK3 Curcumin Xenohormetic Insulin Diabetes Calcium Glutamate NMDAR AMPAR HSP90 inhibitor Consolidation Fidelity Neuron survival Drug discovery Therapy Cognitive function Scaffolding proteins Lipid rafts Synaptic spines Integrin Hippocampus Amyloid BDNF Huntingtin α-Synuclein Parkinson’s Aggregation Herbs GGA CaMKII Calcium channel 

Notes

Acknowledgments

Tim Crul was funded by OTKA PD109539 and Laszlo Vigh and Zsolt Torok by OTKA NK100857 and OTKA NN111006.

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Copyright information

© Cell Stress Society International 2016

Authors and Affiliations

  • Philip L. Hooper
    • 1
    Email author
  • Heather D. Durham
    • 2
  • Zsolt Török
    • 3
  • Paul L. Hooper
    • 4
  • Tim Crul
    • 3
  • László Vígh
    • 3
  1. 1.Division of Endocrinology, Metabolism and Diabetes, Department of MedicineUniversity of Colorado Anschutz Medical CampusAuroraUSA
  2. 2.Department of Neurology/Neurosurgery, Montreal Neurological InstituteMcGill UniversityMontrealCanada
  3. 3.Institute of Biochemistry, Biological Research CenterHungarian Academy of SciencesSzegedHungary
  4. 4.Department of AnthropologyEmory UniversityAtlantaUSA

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