Mis-localization of endogenous TDP-43 leads to ALS-like early-stage metabolic dysfunction and progressive motor deficits.
Yiying HuAlexander HruschaChenchen PanMartina SchiffererMichael K SchmidtBrigitte NuscherMartin GieraSarantos KostidisÖzge BurhanFrauke van BebberDieter EdbauerThomas ArzbergerChristian HaassBettina SchmidPublished in: Molecular neurodegeneration (2024)
The new TDP-43 model mimics the ALS/FTLD hallmark of progressive motor dysfunction. Our results suggest that functional deficits of the hypothalamus, the metabolic regulatory center, might be the primary cause of weight loss in ALS patients. Cytoplasmic gain of function of endogenous TDP-43 leads to metabolic dysfunction in vivo that are reminiscent of early ALS clinical non-motor metabolic alterations. Thus, the CytoTDP zebrafish model offers a unique opportunity to identify mis-regulated targets for therapeutic intervention early in disease progression.
Keyphrases
- amyotrophic lateral sclerosis
- early stage
- weight loss
- multiple sclerosis
- end stage renal disease
- oxidative stress
- traumatic brain injury
- randomized controlled trial
- newly diagnosed
- chronic kidney disease
- transcription factor
- ejection fraction
- peritoneal dialysis
- squamous cell carcinoma
- prognostic factors
- skeletal muscle
- body mass index
- lymph node
- roux en y gastric bypass
- weight gain