A5041443662- Neurogenetic and Muscular Disorders Research
- Neurogenesis and neuroplasticity mechanisms
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Muscle Physiology and Disorders
- Nerve injury and regeneration
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Cerebral Palsy and Movement Disorders
- Cancer-related gene regulation
- ATP Synthase and ATPases Research
- Glycosylation and Glycoproteins Research
- Spinal Cord Injury Research
- Anesthesia and Neurotoxicity Research
Karolinska Institutet
2024
Stockholm University
2024
Centre Interdisciplinaire de Recherche en Biologie
2019-2023
Inserm
2019-2023
Collège de France
2019-2023
Université Paris Sciences et Lettres
2019-2023
Centre National de la Recherche Scientifique
2019-2023
Abstract Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, chromatin organization in recipient cells. ENGRAILED‐1 is one such expressed spinal V1 interneurons that synapse on α‐motoneurons. Neutralizing extracellular by expressing a secreted single‐chain antibody blocks its capture motoneurons resulting α‐motoneuron loss limb weakness. A similar but stronger phenotype observed the Engrailed‐1 heterozygote mouse, confirming...
Abstract Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons (MNs), which innervate skeletal muscles. However, certain MN groups including ocular MNs that regulate eye movement are relatively resilient to ALS. To reveal mechanisms differential susceptibility, we investigate transcriptional dynamics two vulnerable and populations in SOD1G93A ALS mice. Analysis differentially expressed genes (DEGs) shows each neuron type displays a largely...
Abstract Most homeoprotein transcription factors have a highly conserved internalization domain used in intercellular transfer. Internalization of homeoproteins ENGRAILED1 or ENGRAILED2 promotes the survival adult dopaminergic cells, whereas that OTX2 protects retinal ganglion cells. Here we characterize vitro neuroprotective activity several response to H 2 O . Protection is observed with ENGRAILED1, ENGRAILED2, OTX2, GBX2, and LHX9 on midbrain striatal embryonic neurons, cell-permeable...
ABSTRACT Motoneuron degeneration leads to skeletal muscle denervation and impaired motor functions, yet the signals involved remain poorly understood. We find that extracellular ENGRAILED-1, a homeoprotein expressed in spinal cord V1 interneurons synapse on α-motoneurons, has non-cell autonomous activity. Mice heterozygote for Engrailed-1 develop weakness, abnormal reflex partial neuromuscular junction denervation. A single intrathecal injection of ENGRAILED-1 restores innervation, limb...
Abstract Mutations in the RNA/DNA-binding proteins FUS and TDP-43 cause fatal disease amyotrophic lateral sclerosis (ALS). The precise mechanisms behind selective motor neuron degeneration remain unclear it is uncertain if ALS-causative mutations trigger death through shared or distinct pathogenic pathways. To address these two questions, we performed single-cell RNA sequencing across types derived from isogenic induced pluripotent stem cell lines, harbouring P525L, R495X, TARDBP M337V...
ABSTRACT Most homeoprotein transcription factors have a highly conserved internalization domain used in intercellular transfer. Internalization of homeoproteins ENGRAILED1 or ENGRAILED2 promotes the survival adult dopaminergic cells, whereas that OTX2 protects retinal ganglion cells. Here we characterize vitro neuroprotective activity several response to H 2 O . Protection is observed with ENGRAILED1, ENGRAILED2, OTX2, GBX2 and LHX9 on midbrain striatal embryonic neurons cell-permeable c-MYC...
ABSTRACT Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, chromatin organization in recipient cells. ENGRAILED-1 is one such expressed spinal V1 interneurons synapsing on α-motoneurons. Neutralizing extracellular by expressing a secreted single-chain antibody blocks its capture motoneurons resulting α-motoneurons loss limb weakness. A similar but stronger phenotype observed the Engrailed-1 heterozygote mouse, confirming that...