Diana Andrea, Collu Maria, Casu Maria Antonietta, Mocci Ignazia, Aguilar-Santelises Miguel, Setzu Maria Dolores
Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
CNR Institute of Translational Pharmacology, 09010 Pula/Cagliari, Italy.
Brain Sci. 2020 Jan 14;10(1):45. doi: 10.3390/brainsci10010045.
Within neurodegenerative syndromes, Parkinson's disease (PD) is typically associated with its locomotor defects, sleep disturbances and related dopaminergic (DA) neuron loss. The fruit fly, (), with leucine-rich repeat kinase 2 mutants () loss-of-function in the WD40 domain, provides mechanistic insights into corresponding human behaviour, possibly disclosing some physiopathologic features of PD in both genetic and sporadic forms. Moreover, several data support the boosting impact of innate and adaptive immunity pathways for driving the progression of PD. In this context, human dialyzable leukocyte extracts (DLE) have been extensively used to transfer antigen-specific information that influences the activity of various immune components, including inflammatory cytokines. Hence, the main goal of our study was to ascertain the therapeutic potential of DLE from male and female donors on loss-of-function, as compared to wild-type (WT), in terms of rescuing physiological parameters, such as motor and climbing activities, which are severely compromised in the mutant flies. Finally, in search of the anatomical structures responsible for restored functions in parkinsonian-like mutant flies, we found a topographical correlation between improvement of locomotor performances and an increased number of dopaminergic neurons in selective areas of mutant brains.
在神经退行性综合征中，帕金森病（PD）通常与其运动缺陷、睡眠障碍以及相关的多巴胺能（DA）神经元丧失有关。果蝇（）中富含亮氨酸重复激酶2突变体（）在WD40结构域功能丧失，为相应的人类行为提供了机制性见解，可能揭示了遗传和散发性形式的PD的一些生理病理特征。此外，一些数据支持先天免疫和适应性免疫途径对推动PD进展的促进作用。在这种情况下，人可透析白细胞提取物（DLE）已被广泛用于传递影响各种免疫成分（包括炎性细胞因子）活性的抗原特异性信息。因此，我们研究的主要目标是确定与野生型（WT）相比，来自男性和女性供体的DLE对功能丧失的治疗潜力，即在挽救生理参数方面，如运动和攀爬活动，这些参数在突变果蝇中严重受损。最后，为了寻找在帕金森样突变果蝇中负责恢复功能的解剖结构，我们发现运动性能的改善与突变果蝇大脑特定区域多巴胺能神经元数量的增加之间存在地形相关性。
