Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Translational Brain Research, DZNE-German Center for Neurodegenerative Diseases, 81377, Munich, Germany.
Mol Neurodegener. 2023 May 12;18(1):32. doi: 10.1186/s13024-023-00622-7.
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there is currently no disease-modifying treatment to halt neuronal loss in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at the time of the clinical diagnosis, rendering them inaccessible to therapy. Understanding the early pathological changes that precede Lewy body pathology (LBP) and cell loss in PD will likely support the identification of novel diagnostic and therapeutic strategies and help to differentiate LBP-dependent and -independent alterations. Several previous studies identified such specific molecular and cellular changes that occur prior to the appearance of Lewy bodies (LBs) in DA neurons, but a concise map of such early disease events is currently missing.
Here, we conducted a literature review to identify and discuss the results of previous studies that investigated cases with incidental Lewy body disease (iLBD), a presumed pathological precursor of PD.
Collectively, our review demonstrates numerous cellular and molecular neuropathological changes occurring prior to the appearance of LBs in DA neurons.
Our review provides the reader with a summary of early pathological events in PD that may support the identification of novel therapeutic and diagnostic targets and aid to the development of disease-modifying strategies in PD.
帕金森病（PD）是一种进行性神经退行性疾病，与多巴胺能（DA）神经元丧失有关。尽管有对症治疗，但目前尚无能够阻止 PD 神经元丧失的疾病修正治疗方法。开发和测试此类治愈疗法的主要障碍是，在临床诊断时大多数 DA 神经元已经丢失，使得它们无法进行治疗。了解在路易体病理学（LBP）和 PD 细胞丧失之前发生的早期病理变化，可能有助于确定新的诊断和治疗策略，并有助于区分 LBP 依赖性和非依赖性改变。以前的几项研究已经确定了在 DA 神经元中出现路易体（LB）之前发生的这种特定的分子和细胞变化，但目前缺乏这种早期疾病事件的简明图谱。
在这里，我们进行了文献综述，以确定和讨论以前研究的结果，这些研究调查了偶发路易体病（iLBD）的病例，这是 PD 的假定病理前体。
总的来说，我们的综述表明，在 DA 神经元中出现 LB 之前，就已经发生了许多细胞和分子神经病理学变化。
我们的综述为读者提供了 PD 中早期病理事件的总结，这可能有助于确定新的治疗和诊断靶点，并有助于开发 PD 的疾病修正策略。
