Lanza Kathryn, Bishop Christopher
Department of Physiology, Northwestern University, Chicago, IL 60201, USA.
Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
Biomedicines. 2021 Mar 19;9(3):314. doi: 10.3390/biomedicines9030314.
Parkinson's Disease (PD) is characterized by primary and secondary plasticity that occurs in response to progressive degeneration and long-term L-DOPA treatment. Some of this plasticity contributes to the detrimental side effects associated with chronic L-DOPA treatment, namely L-DOPA-induced dyskinesia (LID). The dopamine D3 receptor (D3R) has emerged as a promising target in LID management as it is upregulated in LID. This upregulation occurs primarily in the D1-receptor-bearing (D1R) cells of the striatum, which have been repeatedly implicated in LID manifestation. D3R undergoes dynamic changes both in PD and in LID, making it difficult to delineate D3R's specific contributions, but recent genetic and pharmacologic tools have helped to clarify its role in LID. The following review will discuss these changes, recent advances to better clarify D3R in both PD and LID and potential steps for translating these findings.
帕金森病(PD)的特征在于原发性和继发性可塑性,其发生是对进行性变性和长期左旋多巴治疗的反应。这种可塑性的一些方面导致了与慢性左旋多巴治疗相关的有害副作用,即左旋多巴诱导的运动障碍(LID)。多巴胺D3受体(D3R)已成为LID治疗中有前景的靶点,因为它在LID中上调。这种上调主要发生在纹状体中表达D1受体(D1R)的细胞中,这些细胞反复与LID的表现有关。D3R在PD和LID中都会发生动态变化,这使得难以确定D3R的具体作用,但最近的基因和药理学工具有助于阐明其在LID中的作用。以下综述将讨论这些变化、为更好地阐明PD和LID中的D3R所取得的最新进展以及将这些发现转化应用的潜在步骤。