Abstract

Lewy bodies (LBs) are pathological hallmarks of Parkinson’s disease and dementia with Lewy bodies, characterized by the accumulation of α-synuclein (αSyn) protein in the brain. While LBs were first described a century ago, their formation and morphogenesis mechanisms remain incompletely understood. Here, we present a historical overview of LB definitions and highlight the importance of semantic clarity and precise definitions when describing brain inclusions. Recent breakthroughs in imaging revealed shared features within LB subsets and the enrichment of membrane-bound organelles in these structures, challenging the conventional LB formation model. We discuss the involvement of emerging concepts of liquid-liquid phase separation, where biomolecules demix from a solution to form dense condensates, as a potential LB formation mechanism. Finally, we emphasize the need for the operational definitions of LBs based on morphological characteristics and detection protocols, particularly in studies investigating LB formation mechanisms. A better understanding of LB organization and ultrastructure can contribute to the development of targeted therapeutic strategies for synucleinopathies.

中文翻译：

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路易体的定义：不断变化的定义和不断演变的概念

摘要

路易体 (LB) 是帕金森病和路易体痴呆的病理标志，其特征是 α-突触核蛋白 (αSyn) 蛋白在大脑中积聚。虽然LBs在一个世纪前首次被描述，但它们的形成和形态发生机制仍然不完全清楚。在这里，我们对 LB 定义进行了历史概述，并强调了在描述大脑内含物时语义清晰和精确定义的重要性。最近成像方面的突破揭示了 LB 亚群内的共同特征以及这些结构中膜结合细胞器的富集，挑战了传统的 LB 形成模型。我们讨论了液-液相分离新兴概念的参与，其中生物分子从溶液中分层形成致密冷凝物，作为潜在的 LB 形成机制。最后，我们强调需要基于形态特征和检测协议对 LB 进行操作定义，特别是在研究 LB 形成机制的研究中。更好地了解 LB 组织和超微结构有助于制定针对突触核蛋白病的靶向治疗策略。