黑暗中的谜题：解析蓝斑核神经元中神经黑色素与神经退行性变的关系。
Riddles in the dark: Decoding the relationship between neuromelanin and neurodegeneration in locus coeruleus neurons.
机构信息
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
出版信息
Neurosci Biobehav Rev. 2023 Sep;152:105287. doi: 10.1016/j.neubiorev.2023.105287. Epub 2023 Jun 15.
The noradrenergic locus coeruleus (LC) is among the first regions of the brain affected by pathology in both Alzheimer's disease (AD) and Parkinson's disease (PD), but the reasons for this selective vulnerability are not completely understood. Several features of LC neurons have been proposed as contributing factors to this dysfunction and degeneration, and this review will focus on the presence of neuromelanin (NM). NM is a dark pigment unique to catecholaminergic cells that is formed of norepinephrine (NE) and dopamine (DA) metabolites, heavy metals, protein aggregates, and oxidated lipids. We cover what is currently known about NM and the limitations of historical approaches, then discuss the new human tyrosinase (hTyr) model of NM production in rodent catecholamine cells in vivo that offers unique opportunities for studying its neurobiology, neurotoxicity, and potential of NM-based therapeutics for treating neurodegenerative disease.
蓝斑核（LC）是大脑中最早受到阿尔茨海默病（AD）和帕金森病（PD）病理影响的区域之一，但导致这种选择性易损性的原因尚不完全清楚。LC 神经元的几个特征被认为是导致这种功能障碍和退化的因素，本综述将重点关注神经黑色素（NM）的存在。NM 是一种独特存在于儿茶酚胺能细胞中的深色色素，由去甲肾上腺素（NE）和多巴胺（DA）代谢物、重金属、蛋白质聚集体和氧化脂质组成。我们将介绍目前关于 NM 的知识以及历史方法的局限性，然后讨论新的人类酪氨酸酶（hTyr）在体内啮齿动物儿茶酚胺细胞中产生 NM 的模型，该模型为研究其神经生物学、神经毒性以及基于 NM 的治疗方法治疗神经退行性疾病的潜力提供了独特的机会。
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