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Project

Targeting oxidative stress and metabolic dysfunctionin amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and

fatal neurodegenerative disorder leading to the death of the patient

within three to five years after diagnosis. Oxidative stress and

dysregulated metabolism are both extensively linked to ALS. Given

the lack of efficient treatment possibilities for ALS, this project aims to

elucidate the therapeutic potential of modulating oxidative stress and

metabolic dysfunction in ALS. Therefore, we will target oxidative

stress by inducing metabolic reorientation via prolyl hydroxylase 1

(PHD1) inhibition. PHD1 is an oxygen and metabolite sensor that

rewires energy metabolism. The role and therapeutic potential of

selective PHD1 ablation in ALS are unexplored. We aim to

investigate the effect of PHD1 ablation on ALS disease progression

in different ALS mouse models using genetic approaches and PHD1

antisense oligonucleotides. Single-cell transcriptomics will be

performed to explore the origin of the potential beneficial effects of

PHD1 ablation. Furthermore, we will use state-of-the-art

technologies, such as metabolomics and axonal tracing, in ALS mice

and patient-derived motor neurons to explore the mechanism of

action. This project offers an elegant way to study the role and

therapeutic potential of oxidative stress and energy metabolism using

highly innovative tools which could lead to ground-breaking findings

within the ALS field.

Date:1 Oct 2019 →  Today
Keywords:Amyotrophic lateral sclerosis, energy metabolism, oxidative stress
Disciplines:Neurological and neuromuscular diseases
Project type:PhD project