Dysregulation of Heat Shock Proteins in Neurodegenerative Diseases: Restorative Roles of Small Molecules and Natural Compounds

  • Panchanan Maiti
  • Jayeeta Manna
Part of the Heat Shock Proteins book series (HESP, volume 20)


Gradual depositions of misfolded amyloid proteins play major roles in onset, progression and severity of many neurodegenerative diseases. Several protein clearance machineries exist in the cell which are involved in degradation of these proteins. Therefore, these systems are considered the key players of cellular protein homeostasis. A molecular chaperone, such as heat shock protein (HSP) is one of them, which play a crucial role in degradation of these misfolded protein aggregates. Indeed, larger protein aggregates are degraded by phagocytosis or macroautophagy mechanism, whereas smaller protein aggregates are degraded within the lysosomes with the help of HSP or via ubiquitin proteosomal system. Importantly, the HSPs become dysregulated in different neurodegenerative diseases. Therefore, enhancement of cellular protein quality control machineries, specifically the levels and activities of molecular chaperones could suppress the misfolded protein aggregation and can restore cellular function. Several small molecules and natural polyphenols have been shown to maintain HSP levels in different neurodegenerative diseases. In this book chapter, we discuss the current understanding of the roles of HSPs in protein misfolding neurological diseases, especially on Alzheimer’s, Parkinson’s, Huntington’s, prion diseases and tauopathies. In addition, we also highlighted the modulatory roles of natural polyphenols on HSPs as a therapeutic strategy for protein misfolding neurological diseases.


Chaperone-mediated autophagy Heat shock proteins Molecular chaperones Natural polyphenols Neurodegenerative diseases Ubiquitin system 



Alfa synuclein

Amyloid beta protein


Alzheimer’s disease


Apoptosis-inducing factor


Amyotrophic lateral sclerosis


Amyloid precursor protein


Amyloid precursor protein Sweedis


Adenosine triphosphate




C-terminus of HSC70-interacting protein


Chaperone-mediated autophagy


Central nervous system




Dopamine transporter


Epigallocatechin gallate


Endoplasmic reticulum


Frontotemporal dementia with Parkinsonism


Gambogic acid


Reduced glutathione


Huntington’s disease


HSC70-interacting protein


HSP70-HSP90 organizing protein


Heat shock protein


Heat shock factor


Heat shock element


Lewy bodies


Leucine-rich repeat kinase-2


Mitogen activated protein kinase


Mutant huntingtin


Molecular weight


Nuclear factor kappa beta


Neurofibrillary tangle


Non steroidal anti-inflammatory drugs


Parkinson’s disease


PTEN-induced putative kinase-1




Parts per million


Prion protein


Prion protein cellular form


Prion protein scrapie isoform




Progressive supra-nuclear palsy


Phosphorylated tau


Ribosome-associated complex


Small heat shock protein


Substantia-nigra pars compacta


Superoxide dismutase


Tumor necrosis factor receptor-associated protein-1


Transmissible spongiform encephalopathies


Ubiquitin carboxyl-terminal esterase L1





This work was supported by Veterans Administration and national institute of health and the Cure HD Initiative. We thank Prof. Sally Frautschy, University of California at Los Angeles.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Panchanan Maiti
    • 1
    • 2
    • 3
    • 4
    • 5
  • Jayeeta Manna
    • 6
  1. 1.Field Neurosciences Institute Laboratory for Restorative NeurologyCentral Michigan UniversityMt. PleasantUSA
  2. 2.Program in NeuroscienceCentral Michigan UniversityMt. PleasantUSA
  3. 3.Department of PsychologyCentral Michigan UniversityMt. PleasantUSA
  4. 4.Field Neurosciences InstituteAscension of St. MarySaginawUSA
  5. 5.Brain Research LaboratorySaginaw Valley State UniversitySaginawUSA
  6. 6.Department of Physiology (former)University of Tennessee Health Sciences CenterMemphisUSA

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