Lipid flippase dysfunction as a therapeutic target for endosomal anomalies in Alzheimer's disease

Endosomal anomalies because of vesicular traffic impairment have been indicated as an early pathology of Alzheimer'vertical bar disease (AD). However, the mechanisms and therapeutic targets remain unclear. We previously reported thatbCTF, one of the pathogenic metabolites of APP, interacts with TMEM30A. TMEM30A constitutes a lipid flippase with P4-ATPase and regulates vesicular trafficking through the asymmetric distribution of phospholipids. Therefore, the alteration of lipid flippase activity in AD pathology has got attention. Herein, we showed that the interaction between beta CTF and TMEM30A suppresses the physiological formation and activity of lipid flippase in AD model cells, A7, and App(NLG-F/NLG-F) model mice. Furthermore, the T-RAP peptide derived from the beta CTF binding site of TMEM30A improved endosomal anomalies, which could be a result of the restored lipid flippase activity. Our results provide insights into the mechanisms of vesicular traffic impairment and suggest a therapeutic target for AD

Papillary thyroid microcarcinoma with lung metastases: a case report and review of the literature

Abstract Background Distant metastasis from papillary thyroid microcarcinoma (PTMC) is rare. Here we report a case of PTMC with multiple lung metastases. Case presentation A 64-year-old man presented to our hospital with abdominal pain. Computed tomography incidentally revealed multiple lung nodules. The lung tumor was histologically diagnosed as metastasis of papillary thyroid carcinoma (PTC) by core needle biopsy via thoracoscopy. The patient was referred to our department for further examination. Neck ultrasonography revealed a 0.9 cm hypoechoic nodule in the right lobe of the thyroid gland, which was diagnosed as PTC by fine-needle aspiration cytology. Subsequently, total thyroidectomy was performed, followed by radioiodine therapy. Iodine-131 (131-I) scintigraphy showed a strong accumulation in the lung metastasis. The patient presented no evidence of progression of lung metastasis for 25 months after the operation. Conclusions Lymph node metastasis or extraglandular extension has been reported in the few published cases of metastatic PTMC, including the present case, and the average age of these cases was 58.8 ± 12.0 years. Although active surveillance without surgical resection is expected to become a standard of care for PTMC, this case indicates that a subset of PTMC patients with risk factors may develop distant metastases. Hence, careful preoperative screening is required to avoid complications associated with completion thyroidectomy