A burning question from the first international BPAN symposium: is restoration of autophagy a promising therapeutic strategy for BPAN?

Autor: Mollereau B; Laboratory of Biology and Modelling of the Cell, ENS of Lyon, University of Lyon, University of Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210, UMS 3444 Biosciences Lyon Gerland, Lyon, France., Hayflick SJ; Departments of Molecular and Medical Genetics, Pediatrics, and Neurology, Oregon Health & Science University, Portland, OR, USA., Escalante R; Instituto de Investigaciones Biomédicas Alberto Sols. CSIC-UAM, Madrid, Spain., Mauthe M; Department of Biomedical Sciences of Cells & Systems, Molecular Cell Biology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Papandreou A; Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, University College London Great Ormond Street Institute of Child Health, London, UK.; Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK., Iuso A; Institute of Human Genetics, Technische Universität München, Munich, Germany.; Institute of Neurogenomics, Helmholtz Zentrum München, Neuherberg, Germany., Celle M; Laboratory of Biology and Modelling of the Cell, ENS of Lyon, University of Lyon, University of Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210, UMS 3444 Biosciences Lyon Gerland, Lyon, France., Aniorte S; Laboratory of Biology and Modelling of the Cell, ENS of Lyon, University of Lyon, University of Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210, UMS 3444 Biosciences Lyon Gerland, Lyon, France., Issa AR; Laboratory of Biology and Modelling of the Cell, ENS of Lyon, University of Lyon, University of Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210, UMS 3444 Biosciences Lyon Gerland, Lyon, France., Lasserre JP; Laboratory of NRGEN, Univ. Bordeaux, CNRS, INCIA, UMR 5287, Bordeaux, France., Lesca G; Service de Génétique, Hospices Civils de Lyon, Lyon, France.; Institut Neuromyogene, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, CNRS UMR 5261-INSERM U1315, Université de Lyon - Université Claude Bernard Lyon 1, Lyon, France., Thobois S; Service de Neurologie C, Movement disorders unit, Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.; Institut des Sciences Cognitives Marc Jeannerod, UMR 5229, CNRS, Bron, France.; Faculté de Médecine et de Maieutique Charles Mérieux, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Burger P; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg, INSERM U1258, CNRS UMR7104, Illkirch, France., Walter L; Laboratory of Biology and Modelling of the Cell, ENS of Lyon, University of Lyon, University of Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210, UMS 3444 Biosciences Lyon Gerland, Lyon, France.
Jazyk: angličtina
Zdroj: Autophagy [Autophagy] 2023 Dec; Vol. 19 (12), pp. 3234-3239. Date of Electronic Publication: 2023 Aug 31.
DOI: 10.1080/15548627.2023.2247314
Abstrakt: Beta-propeller protein-associated neurodegeneration (BPAN) is a rare neurodegenerative disease associated with severe cognitive and motor deficits. BPAN pathophysiology and phenotypic spectrum are still emerging due to the fact that mutations in the WDR45 (WD repeat domain 45) gene, a regulator of macroautophagy/autophagy, were only identified a decade ago. In the first international symposium dedicated to BPAN, which was held in Lyon, France, a panel of international speakers, including several researchers from the autophagy community, presented their work on human patients, cellular and animal models, carrying WDR45 mutations and their homologs. Autophagy researchers found an opportunity to explore the defective function of autophagy mechanisms associated with WDR45 mutations, which underlie neuronal dysfunction and early death. Importantly, BPAN is one of the few human monogenic neurological diseases targeting a regulator of autophagy, which raises the possibility that it is a relevant model to directly assess the roles of autophagy in neurodegeneration and to develop autophagy restorative therapeutic strategies for more common disorders. Abbreviations: ATG: autophagy related; BPAN: beta-propeller protein-associated neurodegeneration; ER: endoplasmic reticulum; KO: knockout; NBIA: neurodegeneration with brain iron accumulation; PtdIns3P: phosphatidylinositol-3-phosphate; ULK1: unc-51 like autophagy activating kinase 1; WDR45: WD repeat domain 45; WIPI: WD repeat domain, phosphoinositide interacting.
Databáze: MEDLINE
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