WDR45-dependent impairment of cell cycle in fibroblasts of patients with beta propeller protein-associated neurodegeneration (BPAN)

Biochim Biophys Acta Mol Cell Res. 2024 Dec;1871(8):119842. doi: 10.1016/j.bbamcr.2024.119842. Epub 2024 Sep 13.

Abstract

De novo mutations in the WDR45 gene have been found in patients affected by Neurodegeneration with Brain Iron Accumulation type 5 (NBIA5 or BPAN), with Non-Transferrin Bound Iron (NTBI) accumulation in the basal ganglia and WDR45-dependent impairment of autophagy. Here we show the downregulation of TFEB and cell cycle impairment in BPAN primary fibroblasts. Noteworthy, TFEB overexpression rescued this impairment, depicting a novel WDR45-dependent cell cycle phenotype.

Keywords: Autophagy; Beta-propeller proteinassociated neurodegeneration (BPAN); Cell cycle; Neurodegeneration with brain iron accumulation (NBIA); TFEB; WDR45.

Publication types

  • Letter

MeSH terms

  • Autophagy / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle* / genetics
  • Cells, Cultured
  • Fibroblasts* / metabolism
  • Humans
  • Iron Metabolism Disorders
  • Mutation
  • Neuroaxonal Dystrophies / genetics
  • Neuroaxonal Dystrophies / metabolism
  • Neuroaxonal Dystrophies / pathology

Substances

  • WDR45 protein, human
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Carrier Proteins
  • TFEB protein, human

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)