HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

EFhd2 is a novel amyloid protein associated with pathological tau in Alzheimer's disease.

Abstract
EFhd2 is a conserved calcium-binding protein, abundant within the central nervous system. Previous studies identified EFhd2 associated with pathological forms of tau proteins in the tauopathy mouse model JNPL3, which expresses the human tau(P301L) mutant. This association was validated in human tauopathies, such as Alzheimer's disease (AD). However, the role that EFhd2 may play in tauopathies is still unknown. Here, we show that EFhd2 formed amyloid structures in vitro, a capability that is reduced by calcium ions. Electron microscopy (EM) analyses demonstrated that recombinant EFhd2 formed filamentous structures. EM analyses of sarkosyl-insoluble fractions derived from human AD brains also indicated that EFhd2 co-localizes with aggregated tau proteins and formed granular structures. Immunohistological analyses of brain slices demonstrated that EFhd2 co-localizes with pathological tau proteins in AD brains, confirming the co-aggregation of EFhd2 and pathological tau. Furthermore, EFhd2's coiled-coil domain mediated its self-oligomerization in vitro and its association with tau proteins in JNPL3 mouse brain extracts. The results demonstrate that EFhd2 is a novel amyloid protein associated with pathological tau proteins in AD brain and that calcium binding may regulate the formation of EFhd2's amyloid structures. Hence, EFhd2 may play an important role in the pathobiology of tau-mediated neurodegeneration.
AuthorsYancy Ferrer-Acosta, Eva N Rodríguez-Cruz, François Orange, Hector De Jesús-Cortés, Bismark Madera, Jaime Vaquer-Alicea, Juan Ballester, Maxime J-F Guinel, George S Bloom, Irving E Vega
JournalJournal of neurochemistry (J Neurochem) Vol. 125 Issue 6 Pg. 921-31 (Jun 2013) ISSN: 1471-4159 [Electronic] England
PMID23331044 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Copyright© 2013 International Society for Neurochemistry.
Chemical References
  • Amyloid
  • Amyloidogenic Proteins
  • Calcium-Binding Proteins
  • EFHD2 protein, human
  • EFHD2 protein, mouse
  • tau Proteins
Topics
  • Alzheimer Disease (metabolism, pathology)
  • Amyloid (metabolism)
  • Amyloidogenic Proteins (metabolism)
  • Animals
  • Brain (metabolism, pathology)
  • Calcium-Binding Proteins (metabolism)
  • Humans
  • Mice
  • Mice, Transgenic
  • Neurofibrillary Tangles (metabolism, pathology)
  • Protein Multimerization
  • Protein Structure, Tertiary
  • tau Proteins (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: