14-3-3 Proteins, particularly of the epsilon isoform, are detectable in cerebrospinal fluids of cerebellar diseases in children

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• 作者：Katsunori Fujii^a ; ^{kfujii@faculty.chiba-u.jp} ; Hideki Uchikawa^a ; Yuzo Tanabe^b ; Taku Omata^b ; Ikuya Nonaka^c ; Yoichi Kohno^a
• 关键词：14-3-3 Protein ; Cerebellar disease ; Cerebrospinal fluid (CSF) ; Cerebellar disruption ; Biomarker
• 刊名：Brain and Development
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：35
• 期：6
• 页码：555-560
• 全文大小：791 K

文摘

Background: Detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is a powerful tool for elucidating the mechanisms of neurological disorders. There have been useful studies on 14-3-3 CSF protein detection in Creutzfeldt-Jakob disease and other neurological disorders, but none on cerebellar diseases. Objective: To elucidate whether 14-3-3 CSF proteins are a sensitive biomarker of cerebellar disruption in children. Materials and Methods: We examined 14-3-3 CSF proteins by immunoblotting in seven patients with cerebellar disorders: two with acute cerebellitis, two with acute cerebellar ataxia, and three with cerebellar atrophy. We also investigated 14-3-3 CSF proteins in four cases of febrile seizure and three of influenza-related encephalopathy. Isoforms of 14-3-3 proteins were also identified using isoform-specific antibodies. Results: 14-3-3 proteins were detected in CSF of six patients with cerebellar disorders, the exception being one with acute cerebellar ataxia caused by viral infection. Interestingly, only the 14-3-3 ¦Å isoform was detected in two tested patients with cerebellar involvement. Moreover, longitudinal analysis of 14-3-3 CSF proteins in one patient with infantile neuroaxonal dystrophy showed that the 14-3-3 band density proportionally decreased when the cerebellar atrophy gradually progressed. Another CSF derived from a case of febrile seizure showed no 14-3-3 proteins, whereas all those derived from influenza-related encephalopathy demonstrated 14-3-3 CSF proteins with six isoforms. Conclusions: This is the first report on 14-3-3 CSF proteins as a significant biomarker of cerebellar disruption, as well as other brain diseases. Since 14-3-3 ¦Å is localized in the molecular layer of cerebellum, the unique detection of 14-3-3 ¦Å may indicate cerebellar involvement in the brain.