ISIS Neutron and Muon Source Data Journal

Apoptosis regulating Bcl-2 proteins as an Achilles´ heel in neurodegeneration

Abstract: Neurodegenerative disorders are a significant and growing burden on our society. Despite enormous research efforts there is still a lack of fundamental knowledge about the early molecular processes through which misfolded proteins accumulate and exert their neurotoxic effects. Our main hypothesis is that critical aspects of misfolded protein neurotoxicity act through blocking cell-protecting proteins of the Bcl-2 family, which tightly control the intrinsic programmed cell death (apoptosis) pathway by meeting at the mitochondrial outer mitochondrial membrane (MOM). Here, we seek to prove our hypothesis that the amyloidogenic apoSOD1 protein, a key culprit in the fatal motor neuron disease amyotrophic lateral sclerosis, ALS, can inhibit Bcl-2 directly and/or dissociate the Bcl-2/Bax complex at the MOM with the consequence that Bax gets released and causes neuronal cell death via MOM perforation. This is a potential key mechanism in ALS and other neurodegenerative disorders that is hitherto unexplored. Therefore, we will use NR to provide a molecular and kinetic insight into the interference of apoSOD1 in the recognition of Bcl-2 and sequestering of Bax from its Bcl-2 complex at the membrane level

Principal Investigator: Professor Gerhard Groebner
Experimenter: Dr Jörgen Ådén
Experimenter: Dr Tamás Milán Nagy
Local Contact: Dr Luke Clifton
Experimenter: Dr Hanna Wacklin-Knecht
Experimenter: Dr Sophie Ayscough

DOI: 10.5286/ISIS.E.RB2410460

ISIS Experiment Number: RB2410460

Publisher: STFC ISIS Neutron and Muon Source

Data format: RAW/Nexus
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Data Citation

The recommended format for citing this dataset in a research publication is as:
[author], [date], [title], [publisher], [doi]

For Example:
Professor Gerhard Groebner et al; (2024): Apoptosis regulating Bcl-2 proteins as an Achilles´ heel in neurodegeneration, STFC ISIS Neutron and Muon Source, https://doi.org/10.5286/ISIS.E.RB2410460

Data is released under the CC-BY-4.0 license.