最近的一项突破性研究揭示了精神分裂症的新机制
精神分裂症 is a chronic mental disorder that affects approximately 1.1% of the adult population or roughly 51 million people worldwide. When schizophrenia is in its active form, symptoms can include delusions, hallucinations, disorganized speech or 行为, trouble with thinking, loss of concentration and lack of motivation. Schizophrenia is now widely known but is very poorly understood and its exact cause is still not completely clear. Scientists worldwide believe that a combination of genetics, brain chemistry and environmental factors contributes together towards development and advancement of schizophrenia.These findings have been established after using advanced imaging to look at the brain’s structure and function. Also, schizophrenia cannot be prevented and no cure is available for it, though research is currently happening to develop new and safe treatments.
精神分裂症的早期治疗可能有助于在任何严重并发症发生之前控制症状，并有助于改善患者的长期预后。 如果小心遵循治疗计划，它可以帮助预防复发和症状的极端恶化。 一旦精神分裂症的危险因素明确，有望开发出用于早期诊断和治疗的新型有效疗法。 很长一段时间以来，有人提出大脑中某些天然存在的化学物质（包括称为多巴胺和谷氨酸的神经递质）的问题可能会导致 精神分裂症 and also other mental illnesses. These ‘differences’ are seen in neuroimaging studies on brain and the central nervous system of people who have schizophrenia. The exact significance of these differences or changes is still not very clear, but it definitely indicates that schizophrenia is a 脑 disorder.Schizophrenia requires a lifelong treatment and even in those patients where symptoms appear to have subsided. Generally, a combined treatment of medications and psychosocial therapy can help manage the condition and only in severe cases hospitalization may be needed. A team effort by health professionals is needed in the clinics with expertise in schizophrenia treatment. Most antipsychotic medications for schizophrenia treatment are thought to control symptoms by affecting the brain neurotransmitter dopamine.Unfortunately, manysuch medications tend to cause serious side effects(which can include drowsiness, muscle spasms, dry mouth and blurred vision),making the patients reluctant to take them and in some cases injections may be the chosen route instead of taking a pill.Clearly, to develop therapeutic interventions and drugs to target and treat schizophrenia, it’s important to first understand the disorder by identifying all different possible mechanisms of actions.
一种理解和靶向精神分裂症的新机制
A recent study by neuroscientists from Case Western Reserve University School of 药物, USA,led by Dr. Lin Mei, have uncovered a novel mechanism underlying the cause of schizophrenia. They have used genetic, electrophysiological, biochemical, and molecular techniques to uncover the function of a protein called neuregulin 3 (NRG3). This protein, belonging to the neuregulin protein family, has already been shown to be encoded by a ‘risk’ gene in various other mental illnessesincluding bipolar disordersand depression. And if we talk about schizophrenia, many variations in this particular gene (which encodes for NRG3) are considered as “major risk” factors. Several studies have been done on NRG3, but its exact and detailed physiological function is still very poorly understood.In this new study published in Proceedings of National 科学院研究人员在试图揭示 NRG3 的潜在功能的同时，发现它是精神分裂症的核心，可能成为治疗它的治疗靶点。
Researchers found that NRG3 protein mainly supresses a protein complex – which is very essential for proper neuron communication and the overall efficient working of the brain.The gene which encodes for NRG3 (so that it can effectively perform the function which it has to) was muted in mice in a certain number of neurons of the brain. Specifically, when the mutations were induced in the ‘pyramidal’ neurons – which play an important in activating the brain – mice displayed symptoms and behaviour in line with schizophrenia. The mice had healthy reflexes and also hearing capabilities, but showed unusual level of activity. They showed trouble in remembering (e.g. when navigating mazes) and also acted shy around stranger mice. Thus, it was clear that NRG3 plays a crucial role in schizophrenia and also the type of neurons involved were also defined. Further, researchers also uncovered how exactly this protein NRG3 works at the cellular level. It was seen that it basically inhibits an assembly of a complex of proteins at synapses – the place or junction where nerve cell or neurons communicate. The neurons need a complex (called SNARE, short for Soluble N-ethylmaleimide-sensitive factor activating protein receptor proteins), to transmit neurotransmitters (specifically glutamate) between each other at the synapses. People suffering from severe mental illnesses including schizophrenia, tend to have higher levels of NRG3 蛋白质 这些更高的水平负责抑制谷氨酸的释放——谷氨酸是大脑中天然存在的神经递质。 这在实验室实验中可以看出，NRG3 无法形成“SNARE 复合体”，因此谷氨酸水平因此受到抑制。
谷氨酸在人体内含量丰富，但在大脑中最为突出。 它是我们大脑中高度“刺激”或“兴奋”的神经递质，对激活大脑中的神经元至关重要，因此对我们的学习、理解和记忆至关重要。 该研究得出的结论是，NRG3 对于大脑中适当的谷氨酸传递非常重要，而谷氨酸失衡会导致精神分裂症症状。 此外，这里描述的功能是第一次详细描述，与之前描述的这种特定蛋白质 NRG3 以及属于同一家族的其他蛋白质的作用非常独特。
未来的治疗
精神分裂症是一种非常毁灭性的疾病 心理 illness which drastically affects various areas of life. It disrupts the daily life by affecting day to day functioning, self-care, relationships with family and friends and all kinds of social life. The patients are generally not seen to have a particular ‘psychotic episode’ but rather overall life outlook and balances get affected. Coping with a 心理 disorder as serious as schizophrenia is extremely challenging, both for the person with the condition and for friends and family. Schizophrenia is considered as among the top 10 most disabling conditions. Since schizophrenia is very complex, clinical effect of medications are also varied in different patients and generally do not succeed beyond a few trials. New therapeutic treatments are urgently needed for this condition and this study has shown a new direction towards developing one.
NRG3 蛋白绝对可以作为一种新的治疗靶点，帮助治疗精神分裂症和其他可能的精神疾病，如双相情感障碍和抑郁症。 可以设计出靶向 NRG3 的药物，从而帮助恢复特定类型神经元中的谷氨酸水平，从而恢复精神分裂症期间的大脑功能。 这种方法可以成为一种全新的治疗方法。这项研究揭示了精神分裂症的新细胞机制，并在精神疾病领域产生了巨大的希望。 尽管目前发现和推出有效治疗药物的道路似乎很长，但至少研究方向是正确的。
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来源（S）
王等人。 2018. 通过抑制 SNARE 复合物的组装来控制神经调节蛋白 3 的谷氨酸释放。 美国国家科学院院刊. https://doi.org/10.1073/pnas.1716322115
