TY - JOUR
T1 - Tau Protein Phosphorylated at Threonine-231 is Expressed Abundantly in the Cerebellum in Prion Encephalopathies
AU - Gómez-López, Victor Manuel
AU - Viramontes-Pintos, Amparo
AU - Ontiveros-Torres, Miguel Ángel
AU - Garcés-Ramírez, Linda
AU - De La Cruz, Fidel
AU - Villanueva-Fierro, Ignacio
AU - Bravo-Munõz, Marely
AU - Harrington, Charles R.
AU - Martínez-Robles, Sandra
AU - Yescas, Petra
AU - Guadarrama-Ortíz, Parménides
AU - Hernandes-Alejandro, Mario
AU - Montiel-Sosa, Francisco
AU - Pacheco-Herrero, Mar
AU - Luna-Munõz, José
N1 - Publisher Copyright:
© 2021-The authors. Published by IOS Press.
PY - 2021
Y1 - 2021
N2 - Background: Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called 'prion', which corresponds to a pathological form (PrPSc) of a normal cellular protein (PrPC) expressed in nerve cells. PrPSc is resistant to degradation and can induce abnormal folding of PrPC, and TSEs are characterized by extensive spongiosis and gliosis and the presence of PrPSc amyloid plaques. CJD presents initially with clinical symptoms similar to Alzheimer's disease (AD). In AD, tau aggregates and amyloid-β protein plaques are associated with memory loss and cognitive impairment in patients. Objective: In this work, we study the role of tau and its relationship with PrPSc plaques in CJD. Methods: Multiple immunostainings with specific antibodies were carried out and analyzed by confocal microscopy. Results: We found increased expression of the glial fibrillary acidic protein (GFAP) and matrix metalloproteinase (MMP-9), and an exacerbated apoptosis in the granular layer in cases with prion disease. In these cases, tau protein phosphorylated at Thr-231 was overexpressed in the axons and dendrites of Purkinje cells and the extensions of parallel fibers in the cerebellum. Conclusion: We conclude that phosphorylation of tau may be a response to a toxic and inflammatory environment generated by the pathological form of prion.
AB - Background: Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called 'prion', which corresponds to a pathological form (PrPSc) of a normal cellular protein (PrPC) expressed in nerve cells. PrPSc is resistant to degradation and can induce abnormal folding of PrPC, and TSEs are characterized by extensive spongiosis and gliosis and the presence of PrPSc amyloid plaques. CJD presents initially with clinical symptoms similar to Alzheimer's disease (AD). In AD, tau aggregates and amyloid-β protein plaques are associated with memory loss and cognitive impairment in patients. Objective: In this work, we study the role of tau and its relationship with PrPSc plaques in CJD. Methods: Multiple immunostainings with specific antibodies were carried out and analyzed by confocal microscopy. Results: We found increased expression of the glial fibrillary acidic protein (GFAP) and matrix metalloproteinase (MMP-9), and an exacerbated apoptosis in the granular layer in cases with prion disease. In these cases, tau protein phosphorylated at Thr-231 was overexpressed in the axons and dendrites of Purkinje cells and the extensions of parallel fibers in the cerebellum. Conclusion: We conclude that phosphorylation of tau may be a response to a toxic and inflammatory environment generated by the pathological form of prion.
KW - Cerebellum
KW - neuronal death
KW - prion encephalopathy
KW - prion protein
KW - tau protein
UR - http://www.scopus.com/inward/record.url?scp=85106953972&partnerID=8YFLogxK
U2 - 10.3233/jad-201308
DO - 10.3233/jad-201308
M3 - Artículo
C2 - 33814431
AN - SCOPUS:85106953972
SN - 1387-2877
VL - 81
SP - 769
EP - 785
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -