Impact of POU3F4 mutation on cochlear development and auditory function

Cell Commun Signal. 2025 Mar 5;23(1):121. doi: 10.1186/s12964-025-02133-y. ABSTRACT BACKGROUND: Hearing loss, a major public health issue, affects 1.33 per 1,000 live births worldwide. Genetic factors contribute to over half of congenital cases, with X-linked inheritance accounting for 1-5%. POU3F4 mutations are associated with approximately 50% of X-linked non-syndrome hearing loss cases. POU3F4 plays a […]

Small molecule kinase inhibitor altiratinib inhibits brain cyst forming bradyzoites of Toxoplasma gondii

J Microbiol. 2025 Feb;63(2):e2409001. doi: 10.71150/jm.2409001. Epub 2025 Feb 27. ABSTRACT Chronic toxoplasmosis is caused by Toxoplasma gondii bradyzoites. This study assessed six candidate small molecule kinase inhibitors (SMKIs) against bradyzoites (ME49 strain), the reactivated form of the parasite resulting from the rupture of brain cysts. Bradyzoites were obtained from mouse brain cysts, cultured in […]

Vitamin A treatment restores vision failures arising from Leber’s hereditary optic neuropathy-linked mtDNA mutation

JCI Insight. 2025 Mar 4:e188962. doi: 10.1172/jci.insight.188962. Online ahead of print. ABSTRACT Leber hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy due to mitochondrial DNA (mtDNA) mutations. However, the mechanism underlying retinal cell-specific effects of LHON-linked mtDNA mutations remains poorly understood and there has been no effective treatment or cure for this disorder. […]

Unlocking the genetic blueprint of duchenne muscular dystrophy: A personalized approach with MLPA and WES

Glob Med Genet. 2025 Feb 6;12(2):100038. doi: 10.1016/j.gmg.2025.100038. eCollection 2025 Jun. ABSTRACT BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive X-linked disorder causing muscle degeneration and multisystem involvement, requiring precise genetic diagnosis for timely intervention and treatment. OBJECTIVE: To investigate the genetic landscape of DMD using a two-tiered diagnostic approach combining MLPA and WES, and […]

Stress-induced mitochondrial fragmentation in endothelial cells disrupts blood-retinal barrier integrity causing neurodegeneration

bioRxiv [Preprint]. 2025 Jan 31:2024.12.21.629919. doi: 10.1101/2024.12.21.629919. ABSTRACT Increased vascular leakage and endothelial cell (EC) dysfunction are major features of neurodegenerative diseases. Here, we investigated the mechanisms leading to EC dysregulation and asked whether altered mitochondrial dynamics in ECs impinge on vascular barrier integrity and neurodegeneration. We show that ocular hypertension, a major risk factor […]

Unraveling the role of neuregulin-mediated astrocytes-OPCs axis in the pathogenesis of age-related macular degeneration and Parkinson’s disease

Sci Rep. 2025 Mar 1;15(1):7352. doi: 10.1038/s41598-025-92103-8. ABSTRACT Age-related macular degeneration (AMD) and Parkinson’s disease (PD) are prevalent and debilitating conditions that lead to irreversible blindness and dyskinesia, respectively. Emerging evidences imply that retinal abnormalities may serve as early indicators for monitoring PD. This study endeavors to explore the complex interactions and focus on their […]

PDZK1 regulated by miR-145-5p protects against endothelial cell apoptosis and diabetic retinopathy by targeting mitochondrial function

Exp Eye Res. 2025 Feb 26:110314. doi: 10.1016/j.exer.2025.110314. Online ahead of print. ABSTRACT Mitochondria are a focus of biomedical research because of their role in apoptosis and diabetic retinopathy (DR) initiation and progression. However, the detailed mechanisms underlying mitochondrial disorders and endothelial dysfunction during DR remain elusive. We identified PDZ domain containing 1 (PDZK1) as […]

Rare disease gene association discovery in the 100,000 Genomes Project

Nature. 2025 Feb 26. doi: 10.1038/s41586-025-08623-w. Online ahead of print. ABSTRACT Up to 80% of rare disease patients remain undiagnosed after genomic sequencing1, with many probably involving pathogenic variants in yet to be discovered disease-gene associations. To search for such associations, we developed a rare variant gene burden analytical framework for Mendelian diseases, and applied […]

Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): trial protocol for a pivotal multicentre, randomised double-blind controlled trial

BMJ Open. 2025 Feb 26;15(2):e091495. doi: 10.1136/bmjopen-2024-091495. ABSTRACT INTRODUCTION: Wolfram syndrome (WFS1-Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration […]