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Poster De Conférence Année : 2021

Study of axonal transport in myotonic dystrophy Type 1

Résumé

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease with a global prevalence of 1 in 8000, characterized mainly by muscle, heart and brain involvement, among others. The neurological manifestations vary from executive dysfunction in adults, to attention deficits and low processing speed in pediatric patients, to severe intellectual disability in congenital cases. Cognitive impairment is accompanied by emotional changes, such as social avoidance and anhedonia. Together, the neuropsychological symptoms have an important impact on the quality of life of patients and their families. DM1 is caused by the expansion of a CTG trinucleotide repeat in the 3’UTR of the DMPK gene. Expanded DMPK transcripts are toxic because they form nuclear aggregates which perturb the activity of key RNA-binding proteins, deregulating the processing and expression of hundreds of other genes and transcripts. Despite progress in the understanding of molecular pathogenesis in muscle, the neuronal functions affected and how they lead to the neurological manifestations of DM1 remain unclear, slowing down the development of therapies for the central nervous system. Synaptic transmission and rapid neuronal responses require tightly regulated transport of vesicles inside the neuron. Using a transgenic mouse model of DM1, we have previously found molecular evidence of abnormal vesicle trafficking and axonal transport in DM1. My PhD project builds on from these encouraging results and aims to test whether vesicle dynamics contributes to neuronal and brain dysfunction in DM1. To do so, I am combining molecular methods and high-resolution imaging of living neurons to characterize molecular defects in vesicle-associated proteins and transcripts, and to investigate their functional implications in axonal transport. My project will provide new insight into DM1 disease mechanisms and open new avenues for novel therapies targeting the central nervous system.
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Dates et versions

hal-04009795 , version 1 (01-03-2023)

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  • HAL Id : hal-04009795 , version 1

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Lallemant Louison, Gourdon Genevieve, Mário Gomes-Pereira. Study of axonal transport in myotonic dystrophy Type 1. Journée Boris Ephrussi, May 2021, Paris, France. ⟨hal-04009795⟩
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