| Autor: |
Nonaka W; Department of Neurology, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Takata T; Department of Neurology, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Iwama H; Life Science Research Center, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Komatsubara S; Department of Orthopedic Surgery, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Kobara H; Department of Gastroenterology, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Kamada M; Department of Neurology, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Deguchi K; Department of Neurology, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Touge T; Department of Health Sciences, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Miyamoto O; Department of Medical Engineering, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, Kurashiki, Okayama 701‑0193, Japan., Nakamura T; Department of Physiology 2, Kawasaki Medical School, Kurashiki, Okayama 701‑0192, Japan., Itano T; Department of Neurology, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan., Masaki T; Department of Gastroenterology, Faculty of Medicine, Kagawa University, Miki‑Cho, Kagawa 761‑0793, Japan. |
| Abstrakt: |
Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy described as a syndrome of postural instability, supranuclear vertical gaze palsy, dysarthria, dystonic rigidity of the neck and trunk, dementia, and pseudobulbar palsy. The clinical diagnosis of PSP is often difficult because there are no established biomarkers, and diagnosis is currently based on clinical and imaging findings. Furthermore, the etiology and pathogenesis of PSP remain unknown. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of patients with PSP are rarely reported. The present study aimed to examine cerebrospinal fluid miRNAs, which are considered to be more sensitive indicators of changes in the brain, to elucidate the pathophysiology of PSP and to establish specific biomarkers for diagnosis. The present study used a microarray chip containing 2,632 miRNAs to examine cerebrospinal fluid miRNA expression levels in 11 patients with PSP aged 68‑82 years. A total of 8 age‑ and sex‑matched controls were also included. A total of 38 miRNAs were significantly upregulated and one miRNA was significantly downregulated in the cerebrospinal fluid of patients with PSP. The patients were divided into two groups based on disease stage (early onset and advanced), and changes in miRNA expression were examined. The miRNAs that were most significantly upregulated or downregulated in the early onset group were miR‑204‑3p, miR‑873‑3p and miR‑6840‑5p. The target genes of these miRNAs were associated with molecules related to the ubiquitin‑proteasome system and autophagy pathway. Furthermore, these miRNAs were found to target genes that have been reported to have epigenetic changes following an epigenome‑wide association study of brain tissues of patients with PSP. This suggested that these miRNAs and genes may have some involvement in the pathogenesis of PSP. However, the sample size of the present study was small; therefore, a greater number of patients with PSP should be examined in future studies. |
