Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders
Katrin Linda, Elly Lewerissa, Anouk H. A. Verboven, Michele Gabriele, Monica Frega, Teun M. Klein Gunnewiek, Lynn Devilée, Edda Ulferts, Marina P. Hommersom, Astrid Oudakker, Chantal Schoenmaker, Hans van Bokhoven, Dirk Schubert, Giuseppe Testa, David A. Koolen, Bert B.A. de Vries, Nael Nadif Kasri
Abstract
; BSO: buthionine sulfoximine; CV: coefficient of variation; DIV: days in vitro; H4K16ac: histone 4 lysine 16 acetylation; iPSC: induced-pluripotent stem cell; KANSL1: KAT8 regulatory NSL complex subunit 1; KdVS: Koolen-de Vries Syndrome; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MEA: micro-electrode array; MTOR: mechanistic target of rapamycin kinase; NSL complex: nonspecific lethal complex; 8-oxo-dG: 8-hydroxydesoxyguanosine; RAP: rapamycin; ROS: reactive oxygen species; sEPSCs: spontaneous excitatory postsynaptic currents; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; SYN: synapsin; WRT: wortmannin.