Neuronal glucose metabolism in amyotrophic lateral sclerosis

von Jana Sophia Dannenberg
Dissertation
Datum der mündl. Prüfung:2024-06-27
Erschienen:2024-06-28
Betreuer:PD Dr. Jan C. Koch
Gutachter:PD Dr. Jan C. Koch
Gutachter:Prof. Dr. Michael Thumm
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-10548

 

 

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Englisch

ALS is a rapidly progressing neurodegenerative disease characterized by motor neuron death ultimately leading to paralysis and respiratory failure. While a great deal of progress has been made deciphering the underlying pathogenic pathways, no curative therapy is available today. Over the last few decades, alterations in energy homeostasis and glucose metabolism have emerged as common features across many different forms of ALS. Disturbed energy homeostasis and a general hypermetabolism are observed in ALS patients even before motor symptoms begin, suggesting it to be an early and possibly causative factor in disease progression. A regional glucose hypometabolism in ALS-associated brain regions has been shown by various studies, but data illuminating the molecular level is still scarce. This study examines the expression and activity of key glucose metabolism enzymes both in-vitro in a TDP-43 (wildtype and M337V mutation) overexpression cortical neuron cell culture as well as in-vivo analyzing serum and CSF of ALS patients compared to controls. The observed decrease in enzyme activity in-vitro and decreased enzyme expression in-vivo support the hypothesis of glucose hypometabolism and strengthen the role of energy metabolism playing a part in future ALS diagnostics and therapy.
Keywords: ALS; Energy metabolism; Glucose metabolism; Glycolysis; CSF; Serum; Enzyme expression; Enzyme activity; AMPK; Western blot; TDP-43
 
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