PMID- 31205424
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1179-0695 (Print)
IS  - 1179-0695 (Electronic)
IS  - 1179-0695 (Linking)
VI  - 13
DP  - 2019
TI  - A Mechanism for the Development of Chronic Traumatic Encephalopathy From 
      Persistent Traumatic Brain Injury.
PG  - 1179069519849935
LID - 10.1177/1179069519849935 [doi]
LID - 1179069519849935
AB  - A mechanism that describes the progression of traumatic brain injury (TBI) to 
      end-stage chronic traumatic encephalopathy (CTE) is offered in this article. This 
      mechanism is based upon the observed increase in the concentration of both tau 
      protein and of human leukocyte antigen (HLA) class I proteins; the HLA increase 
      is expressed on the cell membrane of neural cells. These events follow the 
      inflammatory responses caused by the repetitive TBI. Associated inflammatory 
      changes include macrophage entry into the brain parenchyma from increased 
      permeability of the blood-brain barrier (BBB) and microglial activation at the 
      base of the sulci. The release of interferon gamma from the microglia and 
      macrophages induces the marked increased expression of HLA class I proteins by 
      the neural cells and subsequent redistribution of the tau proteins to the glial 
      and neuronal surface. In those individuals with highly expressed HLA class I C, 
      the high level of HLA binds tau protein electrostatically. The ionic region of 
      HLA class I C (amino acid positions 50-90) binds to the oppositely charged ionic 
      region of tau (amino acid positions 93-133). These interactions thereby shift the 
      cellular localization of the tau and orient the tau spatially so that the 
      cross-linking sites of tau (275-280 and 306-311) are aligned. This alignment 
      facilitates the cross-linking of tau to form the intracellular and extracellular 
      microfibrils of tau, the primary physiological characteristic of tauopathy. 
      Following endocytosis of the membrane HLA/tau complex, these microfibrils 
      accumulate and produce a tau-storage-like disease. Therefore, tauopathy is the 
      secondary collateral process of brain injury, resulting from the substantial 
      increase in tau and HLA expression on neural cells. This proposed mechanism 
      suggests several potential targets for mitigating the clinical progression of TBI 
      to CTE.
FAU - Demock, Melissa
AU  - Demock M
AD  - Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
FAU - Kornguth, Steven
AU  - Kornguth S
AUID- ORCID: 0000-0002-3709-0359
AD  - Departments of Neurology and Kinesiology and Health Education, The University of 
      Texas at Austin, Austin, TX, USA.
AD  - Departments of Neurology and Biomolecular Chemistry, University of 
      Wisconsin-Madison, Madison, WI, USA.
LA  - eng
PT  - Journal Article
DEP - 20190520
PL  - United States
TA  - J Exp Neurosci
JT  - Journal of experimental neuroscience
JID - 101517658
PMC - PMC6537483
OTO - NOTNLM
OT  - Human Leukocyte Antigen
OT  - Traumatic brain injury
OT  - chronic traumatic encephalopathy
OT  - electrostatic binding
OT  - major histocompatibility complex
OT  - protein-protein interaction
OT  - tau protein
OT  - tauopathy
COIS- Declaration of conflicting interests:The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2019/06/18 06:00
MHDA- 2019/06/18 06:01
PMCR- 2019/05/20
CRDT- 2019/06/18 06:00
PHST- 2019/02/14 00:00 [received]
PHST- 2019/04/22 00:00 [accepted]
PHST- 2019/06/18 06:00 [entrez]
PHST- 2019/06/18 06:00 [pubmed]
PHST- 2019/06/18 06:01 [medline]
PHST- 2019/05/20 00:00 [pmc-release]
AID - 10.1177_1179069519849935 [pii]
AID - 10.1177/1179069519849935 [doi]
PST - epublish
SO  - J Exp Neurosci. 2019 May 20;13:1179069519849935. doi: 10.1177/1179069519849935. 
      eCollection 2019.