Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases.

The endoplasmic reticulum, a key cellular organelle, regulates a wide variety of cellular activities. Endoplasmic reticulum autophagy, one of the quality control systems of the endoplasmic reticulum, plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover, remodeling, and proteostasis. In this review, we briefly describe the endoplasmic reticulum quality control system, and subsequently focus on the role of endoplasmic reticulum autophagy, emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements. We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases. In summary, this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders. This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

GPR50 regulates neuronal development as a mitophagy receptor.

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

Furazolidone-induced pulmonary toxicity in Helicobacter pylori infection: Two case reports.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a global problem, causing significant morbidity and mortality. Furazolidone is recommended to eradicate H. pylori infections in China owing to the highly associated antibiotic resistance. CASE SUMMARY: This article presents two cases of lung injury caused by furazolidone treatment of H. pylori infection and the relevant literature review. Two patients developed symptoms, including fever, cough, and fatigue after receiving a course of furazolidone for H. pylori infection. Chest computed tomography showed bilateral interstitial infiltrates. Laboratory studies revealed elevated blood eosinophil count. After discontinuing furazolidone with or without the use of corticosteroids, the symptoms improved rapidly. A PubMed database literature search revealed three reported cases of lung injury suggestive of furazolidone-induced pulmonary toxicity. CONCLUSION: Clinicians should be aware of the side effects associated with the administration of furazolidone to eradicate H. pylori infection.

Feasibility and Safety of Neoadjuvant Alectinib in Pulmonary Invasive Mucinous Adenocarcinoma with ALK Rearrangement: Case Report and Literature Review.

BACKGROUND: Pulmonary invasive mucinous adenocarcinoma (IMA) is a rare variant of lung adenocarcinoma that rarely shows anaplastic lymphoma kinase (ALK) rearrangement. Alectinib (tyrosine kinase inhibitors) has been listed as category 1 recommendations for advanced ALK + NSCLC first-line therapy due to low toxicity and excellent efficacy, and its median progression-free survival is 34.8 months. Here, we report a case of a patient with ALK-rearranged lung IMA who showed favorable results to neoadjuvant alectinib. CASE: A 67-year-old man with no history of smoking was diagnosed with clinical stage as IIIB invasive mucinous adenocarcinoma based on clinical symptoms, chest CT and pathological findings. The anaplastic lymphoma kinase (ALK) fusion status was assessed by real-time PCR. After acquiring informed consent from the patient, we offered neoadjuvant alectinib at a dosage of 150 mg twice per day for three cycles (84 days), all lesions were undetectable on chest CT. Later, a thoracoscopic left lobectomy was performed. The postoperative pathological showed that a small amount of tumor cells remained, and the TNM stage was downstaged as T1aN0M0 IA. CONCLUSION: To our knowledge, this is the first case discussing the treatment of ALK-rearranged IMA of the lung with neoadjuvant alectinib. Alectinib is an effective ALK inhibitor, and in cases of lung adenocarcinoma with ALK rearrangement, alectinib treatment is a reasonable and priority option. Neoadjuvant alectinib may be clinically feasible and well tolerated in locally advanced NSCLC.