Biological links between traumatic brain injury and Parkinson's disease

• Published in: Acta neuropathologica communications Vol. 8; no. 1; p. 45
• Main Authors: Delic, Vedad, Beck, Kevin D, Pang, Kevin C H, Citron, Bruce A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07-04-2020; BioMed Central; BMC
• Subjects: alpha-Synuclein - metabolism; Amyloid beta-protein; Amyloid beta-Protein Precursor - metabolism; Analysis; Animals; B cells; Blood-Brain Barrier - metabolism; Brain; Brain damage; Brain injuries; Brain Injuries, Traumatic - epidemiology; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Disease; DNA-Binding Proteins - metabolism; Energy Metabolism; Humans; Hypotheses; Inflammation; Inflammation - metabolism; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - metabolism; Mutation; Nervous system; Neurodegeneration; Neurons; Neuropathology; Parkinson Disease - epidemiology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Pathogens; Pathology; Phosphorylation; Protein Aggregation, Pathological - metabolism; Protein binding; rab GTP-Binding Proteins - metabolism; Review; Risk; Risk factors; Studies; tau Proteins - metabolism; Traumatic brain injury; Tremor; Up-Regulation; United States > US
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-020-00924-7

Parkinson's Disease (PD) is a progressive neurodegenerative disorder with no cure. Clinical presentation is characterized by postural instability, resting tremors, and gait problems that result from progressive loss of A9 dopaminergic neurons in the substantia nigra pars compacta. Traumatic brain injury (TBI) has been implicated as a risk factor for several neurodegenerative diseases, but the strongest evidence is linked to development of PD. Mild TBI (mTBI), is the most common and is defined by minimal, if any, loss of consciousness and the absence of significant observable damage to the brain tissue. mTBI is responsible for a 56% higher risk of developing PD in U.S. Veterans and the risk increases with severity of injury. While the mounting evidence from human studies suggests a link between TBI and PD, fundamental questions as to whether TBI nucleates PD pathology or accelerates PD pathology in vulnerable populations remains unanswered. Several promising lines of research point to inflammation, metabolic dysregulation, and protein accumulation as potential mechanisms through which TBI can initiate or accelerate PD. Amyloid precursor protein (APP), alpha synuclein (α-syn), hyper-phosphorylated Tau, and TAR DNA-binding protein 43 (TDP-43), are some of the most frequently reported proteins upregulated following a TBI and are also closely linked to PD. Recently, upregulation of Leucine Rich Repeat Kinase 2 (LRRK2), has been found in the brain of mice following a TBI. Subset of Rab proteins were identified as biological substrates of LRRK2, a protein also extensively linked to late onset PD. Inhibition of LRRK2 was found to be neuroprotective in PD and TBI models. The goal of this review is to survey current literature concerning the mechanistic overlap between TBI and PD with a particular focus on inflammation, metabolic dysregulation, and aforementioned proteins. This review will also cover the application of rodent TBI models to further our understanding of the relationship between TBI and PD.