Kajian terobosan baru-baru ini menemui mekanisme baru skizofrenia
Schizophrenia 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 tingkah laku, 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.
Rawatan awal skizofrenia boleh membantu mengawal simptom sebelum sebarang komplikasi serius berlaku dan boleh membantu memperbaiki hasil jangka panjang bagi pesakit. Jika pelan rawatan diikuti dengan berhati-hati, ia boleh membantu mencegah kambuh dan juga gejala yang lebih teruk. Terapi baharu dan berkesan untuk diagnosis dan rawatan awal boleh diharapkan dapat dibangunkan setelah faktor risiko skizofrenia jelas. Telah dicadangkan sejak sekian lama bahawa masalah dengan bahan kimia semulajadi tertentu di dalam otak - termasuk neurotransmitter yang dipanggil dopamin dan glutamat - boleh menyumbang kepada skizofrenia 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 otak 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.
Mekanisme baru untuk memahami dan menyasarkan skizofrenia
A recent study by neuroscientists from Case Western Reserve University School of Perubatan, 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 Akademi Sains, penyelidik semasa cuba untuk mendedahkan potensi fungsi NRG3, mendapati bahawa ia adalah pusat kepada skizofrenia dan boleh menjadi sasaran terapeutik yang mungkin untuk merawatnya.
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 protein soya dan tahap yang lebih tinggi ini bertanggungjawab untuk menyekat pembebasan glutamat - neurotransmitter yang berlaku secara semula jadi di dalam otak. Ini dilihat dalam eksperimen makmal bahawa NRG3 tidak dapat membentuk 'kompleks SNARE' dan oleh itu tahap glutamat ditindas akibat daripada ini.
Glutamat banyak terdapat dalam tubuh manusia tetapi paling ketara ditemui di otak. Ia adalah neurotransmitter yang sangat 'stimulatory' atau 'excitatory' dalam otak kita dan paling kritikal untuk mengaktifkan neuron di otak dan dengan itu penting untuk pembelajaran, pemahaman dan ingatan kita. Kajian ini menyimpulkan bahawa NRG3 adalah sangat penting untuk penghantaran glutamat yang betul di otak dan ketidakseimbangan glutamat menyebabkan gejala skizofrenia. Juga, fungsi yang diterangkan di sini diperincikan buat kali pertama dan sangat unik daripada peranan sebelumnya yang diterangkan tentang proteinNRG3 tertentu ini serta protein lain yang dimiliki oleh keluarga yang sama.
Terapi pada masa hadapan
Skizofrenia adalah penyakit yang sangat dahsyat mental 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 mental 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.
Protein NRG3 pasti boleh berfungsi sebagai sasaran terapeutik baharu untuk membantu merawat skizofrenia dan mungkin penyakit mental lain seperti bipolar dan kemurungan. Dadah boleh direka bentuk yang boleh menyasarkan NRG3 dengan itu membantu memulihkan tahap glutamat dalam jenis neuron tertentu dan dengan itu memulihkan fungsi otak semasa skizofrenia. Metodologi ini boleh menjadi pendekatan yang sama sekali baru ke arah rawatan. Kajian ini telah menjelaskan mekanisme selular baru skizofrenia dan telah menjana harapan yang besar dalam bidang penyakit mental. Walaupun jalan untuk menemui dan melancarkan ubat-ubatan yang berkesan untuk rawatan nampaknya kelihatan sangat lama pada masa ini, penyelidikan berada dalam arah yang betul sekurang-kurangnya.
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{Anda boleh membaca kertas penyelidikan asal dengan mengklik pautan DOI yang diberikan di bawah dalam senarai sumber yang dipetik}
Sumber (s)
Wang et al. 2018. Mengawal pembebasan glutamat oleh neuregulin3 melalui menghalang pemasangan kompleks SNARE. Prosiding Akademi Sains Kebangsaan. https://doi.org/10.1073/pnas.1716322115
