Increased Risk of Aging-Related Neurodegenerative Disease after Traumatic Brain Injury

被引:22
作者
Barker, Sarah [1 ,2 ,3 ,4 ,5 ]
Paul, Bindu D. D. [6 ,7 ,8 ,9 ]
Pieper, Andrew A. A. [1 ,2 ,3 ,4 ,5 ,10 ,11 ]
机构
[1] Univ Hosp, Harrington Discovery Inst, Ctr Brain Hlth Med, Cleveland Med Ctr, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA
[3] Louis Stokes Cleveland VA Med Ctr, Geriatr Psychiat, GRECC, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Inst Transformat Mol Med, Sch Med, Cleveland, OH 44106 USA
[5] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA
[6] Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Sch Med, Baltimore, MD 21211 USA
[7] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Baltimore, MD 21211 USA
[8] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21211 USA
[9] Lieber Inst Brain Dev, Baltimore, MD 21205 USA
[10] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA
[11] Cleveland Alzheimers Dis Res Ctr, Translat Therapeut Core, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
traumatic brain injury; neurodegeneration; dementia; amyotrophic lateral sclerosis; frontotemporal dementia; Parkinson's disease; Alzheimer's disease; oxidative stress; proteostasis; neuroinflammation; AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID-BETA ACCUMULATION; HEAT-SHOCK-PROTEIN; UBIQUITIN PROTEASOME SYSTEM; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; PRECURSOR PROTEIN; MOUSE MODEL; FRONTOTEMPORAL DEMENTIA;
D O I
10.3390/biomedicines11041154
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Traumatic brain injury (TBI) survivors frequently suffer from chronically progressive complications, including significantly increased risk of developing aging-related neurodegenerative disease. As advances in neurocritical care increase the number of TBI survivors, the impact and awareness of this problem are growing. The mechanisms by which TBI increases the risk of developing aging-related neurodegenerative disease, however, are not completely understood. As a result, there are no protective treatments for patients. Here, we review the current literature surrounding the epidemiology and potential mechanistic relationships between brain injury and aging-related neurodegenerative disease. In addition to increasing the risk for developing all forms of dementia, the most prominent aging-related neurodegenerative conditions that are accelerated by TBI are amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson's disease (PD), and Alzheimer's disease (AD), with ALS and FTD being the least well-established. Mechanistic links between TBI and all forms of dementia that are reviewed include oxidative stress, dysregulated proteostasis, and neuroinflammation. Disease-specific mechanistic links with TBI that are reviewed include TAR DNA binding protein 43 and motor cortex lesions in ALS and FTD; alpha-synuclein, dopaminergic cell death, and synergistic toxin exposure in PD; and brain insulin resistance, amyloid beta pathology, and tau pathology in AD. While compelling mechanistic links have been identified, significantly expanded investigation in the field is needed to develop therapies to protect TBI survivors from the increased risk of aging-related neurodegenerative disease.
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页数:25
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