In this report, we describe unilateral medial pontomedullary junction (MPMJ) syndrome as a novel brain stem stroke syndrome. A 68-year-old woman suddenly developed vertigo, ipsilateral facial paresis, contralateral thermal hypoalgesia (TH) and dysphagia without lateral gaze palsy, curtain sign and hoarseness. Magnetic resonance (MR) imaging showed a small infarction at the right MPMJ. MR angiography did not show vertebrobasilar arterial dissection, thrombosis or vasospasm. Finally, her dysphagia regressed over 4 weeks in synchronization with recovery of TH. To the best of our knowledge and based on a review of the literature, this MPMJ syndrome associated with the unilateral MPMJ infarction is a novel brain stem stroke syndrome different from Foville syndrome, Millard–Gubler syndrome, Wallenberg syndrome or Dejerine’s syndrome. In the MPMJ syndrome, transient, albeit severe, dysphagia based on the TH-impaired swallowing reflex bothered the patient more than hemiparesthesia of TH did.
NRF2 is a transcription factor responsible for antioxidant stress responses that is usually regulated in a redox‐dependent manner. p62 bodies formed by liquid–liquid phase separation contain Ser349‐phosphorylated p62, which participates in the redox‐independent activation of NRF2. However, the regulatory mechanism and physiological significance of p62 phosphorylation remain unclear. Here, we identify ULK1 as a kinase responsible for the phosphorylation of p62. ULK1 colocalizes with p62 bodies, directly interacting with p62. ULK1‐dependent phosphorylation of p62 allows KEAP1 to be retained within p62 bodies, thus activating NRF2. p62S351E/+ mice are phosphomimetic knock‐in mice in which Ser351, corresponding to human Ser349, is replaced by Glu. These mice, but not their phosphodefective p62S351A/S351A counterparts, exhibit NRF2 hyperactivation and growth retardation. This retardation is caused by malnutrition and dehydration due to obstruction of the esophagus and forestomach secondary to hyperkeratosis, a phenotype also observed in systemic Keap1‐knockout mice. Our results expand our understanding of the physiological importance of the redox‐independent NRF2 activation pathway and provide new insights into the role of phase separation in this process.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.