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Neurodevelopmental disorders: metallomics studies for the identification of potential biomarkers associated to diagnosis and treatment
Journal of Trace Elements in Medicine and Biology ( IF 3.5 ) Pub Date : 2020-03-16 , DOI: 10.1016/j.jtemb.2020.126499
Catia Scassellati , Cristian Bonvicini , Luisa Benussi , Roberta Ghidoni , Rosanna Squitti

Background

Diagnosis and treatment of complex diseases such as Neurodevelopmental Disorders (NDDs) can be resolved through the identification of biomarkers. Metallomics (research on biometals) and metallomes (metalloproteins/metalloenzymes/chaperones) along with genomics, proteomics andmetabolomics, can contribute to accelerate and improve this process.

Aim

This review focused on five NDDs pathologies (Schizophrenia, SZ; Attention Deficit Hyperactivity Disorder, ADHD; Autism, ADS; Epilepsy), and we reported, for the first time, different studies on the role played by the principal six essential trace elements (Cobalt, Co; Copper, Cu; Iron, Fe; Manganese, Mn; Selenium, Se; Zinc, Zn) that can influence diagnosis/treatment.

Results

in light of the literature presented, based on meta-analyses, we suggest that, Zn (glutamatergic neurotransmission, inflammation, neurodegeneration, autoimmunity alterations), could be a potential diagnostic biomarker associated to SZ. Moreover, considering the single association studies going in the same direction, increased Cu (catecholamine alterations, glucose intolerance, altered lipid metabolism/oxidative stress) and lower Fe (dopaminergic dysfunctions) levels were associated with a specific negative symptomatology. Lower Mn (lipid metabolism/oxidative stress alterations), and lower Se (metabolic syndrome) were linked to SZ. From the meta-analyses in ADHD, it is evidenced that Fe (and ferritin in particular), Mn, and Zn (oxidative stress dysfunctions) could be potential diagnostic biomarkers, mainly associated to severe hyperactive or inattentive symptoms; as well as Cu, Fe, Zn in ADS and Zn in Epilepsy.

Fe, Zn and Mn levels seem to be influenced by antipsychotics treatment in SZ; Mn and Zn by methylphenidate treatment in ADHD; Cu and Zn by antiepileptic drugs in Epilepsy.

Conclusions

Although there is controversy and further studies are needed, this work summarizes the state of art of the literature on this topic. We claim to avoid underreporting the impact of essential trace elements in paving the way for biomarkers research for NDDs.



中文翻译:

神经发育障碍:金属组学研究,以鉴定与诊断和治疗相关的潜在生物标志物

背景

复杂疾病如神经发育障碍(NDD)的诊断和治疗可以通过生物标志物的鉴定来解决。金属组学(生物金属研究)和金属组(金属蛋白/金属酶/分子伴侣)以及基因组学,蛋白质组学和代谢组学可以促进和改善这一过程。

目标

这篇综述集中于五种NDD病理学(精神分裂症,深圳,注意力缺陷多动障碍,多动症,自闭症,ADS,癫痫病),并且我们首次报道了关于主要六种基本微量元素(钴的作用)的不同研究。 ,钴,铜,铜,铁,铁,锰,锰,硒,锌,锌)可能会影响诊断/治疗。

结果

根据提供的文献,基于荟萃分析,我们认为Zn(谷氨酸能神经传递,炎症,神经退行性变,自身免疫性改变)可能是与SZ相关的潜在诊断生物标志物。此外,考虑到单一关联研究朝着相同的方向发展,Cu(儿茶酚胺改变,葡萄糖耐受不良,脂质代谢/氧化应激改变)和Fe(多巴胺能功能障碍)水平降低与特定的阴性症状相关。较低的锰(脂质代谢/氧化应激改变)和较低的硒(代谢综合征)与SZ有关。从多动症的荟萃分析可以证明,铁(尤其是铁蛋白),锰和锌(氧化应激功能障碍)可能是潜在的。诊断性生物标志物,主要与严重的过度活跃或注意力不集中的症状有关;以及ADS中的Cu,Fe,Zn和癫痫病中的Zn。

在深圳,抗精神病药物治疗似乎会影响铁,锌和锰的含量;在ADHD中通过哌醋甲酯处理的锰和锌;铜和锌可通过抗癫痫药治疗癫痫。

结论

尽管存在争议并需要进一步的研究,但这项工作总结了有关该主题的最新文献。我们声称在为NDDs的生物标志物研究铺平道路时,应避免少报必要的微量元素的影响。

更新日期:2020-03-16
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