Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin.
The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer's disease, tauopathies, and Huntington's diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell.
Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Panchanan
0000-0001-5151-3330
P
Maiti
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Jayeeta
0000-0002-2839-510X
J
Manna
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shobi
0000-0002-9653-6939
S
Veleri
Veteran's Greater Los Angeles Healthcare System, Geriatric Research and Educational Core, Los Angeles, CA 90073, USA ; Departments of Neurology and Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Sally
S
Frautschy
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003474:Curcumin / Q000627:therapeutic use*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018832:Molecular Chaperones / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D025801:Ubiquitin; D003474:Curcumin