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.

中文翻译：

---

外伤性脑损伤与帕金森病之间的生物学联系。

帕金森病 (PD) 是一种无法治愈的进行性神经退行性疾病。临床表现的特点是姿势不稳、静止性震颤和步态问题，这是由于黑质致密部中 A9 多巴胺能神经元的进行性丧失引起的。创伤性脑损伤 (TBI) 被认为是多种神经退行性疾病的危险因素，但最有力的证据与 PD 的发展有关。轻度 TBI (mTBI) 是最常见的，其定义是意识丧失（如果有的话）和对脑组织没有明显的明显损伤。mTBI 导致美国退伍军人患 PD 的风险高出 56%，并且风险随着受伤的严重程度而增加。虽然来自人类研究的越来越多的证据表明 TBI 和 PD 之间存在联系，关于 TBI 是否会导致 PD 病理学成核或加速易感人群的 PD 病理学的基本问题仍未得到解答。几个有希望的研究方向将炎症、代谢失调和蛋白质积累作为 TBI 启动或加速 PD 的潜在机制。淀粉样前体蛋白 (APP)、α 突触核蛋白 (α-syn)、过度磷酸化的 Tau 和 TAR DNA 结合蛋白 43 (TDP-43) 是一些最常报道的在 TBI 后上调的蛋白质，并且也密切相关到 PD。最近，在 TBI 后小鼠的大脑中发现了富含亮氨酸重复激酶 2 (LRRK2) 的上调。Rab 蛋白的子集被鉴定为 LRRK2 的生物底物，LRRK2 是一种与晚发性 PD 广泛相关的蛋白质。发现抑制 LRRK2 在 PD 和 TBI 模型中具有神经保护作用。本综述的目的是调查当前关于 TBI 和 PD 之间机制重叠的文献，特别关注炎症、代谢失调和上述蛋白质。本综述还将涵盖啮齿动物 TBI 模型的应用，以进一步了解 TBI 与 PD 之间的关系。