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Neuropharmacology. 2019 Feb;145(Pt B):160-176. doi: 10.1016/j.neuropharm.2018.06.021. Epub 2018 Jun 20.

Novel therapies for combating chronic neuropathological sequelae of TBI.

Author information

1
Geriatric Research Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: ikonomovicmd@upmc.edu.
2
Geriatric Research Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
3
Geriatric Research Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA; Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Abstract

Traumatic brain injury (TBI) is a risk factor for development of chronic neurodegenerative disorders later in life. This review summarizes the current knowledge and concepts regarding the connection between long-term consequences of TBI and aging-associated neurodegenerative disorders including Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and Parkinsonism, with implications for novel therapy targets. Several aggregation-prone proteins such as the amyloid-beta (Aβ) peptides, tau proteins, and α-synuclein protein are involved in secondary pathogenic cascades initiated by a TBI and are also major building blocks of the hallmark pathological lesions in chronic human neurodegenerative diseases with dementia. Impaired metabolism and degradation pathways of aggregation-prone proteins are discussed as potentially critical links between the long-term aftermath of TBI and chronic neurodegeneration. Utility and limitations of previous and current preclinical TBI models designed to study the link between TBI and chronic neurodegeneration, and promising intervention pharmacotherapies and non-pharmacologic strategies to break this link, are also summarized. Complexity of long-term neuropathological consequences of TBI is discussed, with a goal of guiding future preclinical studies and accelerating implementation of promising therapeutics into clinical trials. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".

KEYWORDS:

Alpha synuclein; Alzheimer's disease; Amyloid; Brain trauma; Chronic traumatic encephalopathy; Tau

PMID:
29933008
PMCID:
PMC6513317
[Available on 2020-02-01]
DOI:
10.1016/j.neuropharm.2018.06.021
[Indexed for MEDLINE]

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