ISIS Neutron and Muon Source Data Journal

Apoptosis regulating Bcl-2 protein family at the mitochondrial membrane: Its function in neurodegeneration

Abstract: Programmed cell death (apoptosis) is essential for human life. Its intrinsic pathway is regulated by opposing members of the Bcl-2 protein family who tightly controls mitochondrial outer membrane (MOM) pore formation and release of apoptotic factors triggering cell death. Escape of apoptosis by blocking cell killing Bax (a Bcl-2 member) protein induced MOM perforation is an important hallmark of many cancers. Here, our main hypothesis is that in neurodegenerative disorders premature neuronal death occurs through blocking cell-protecting Bcl-2 protein (and relatives) by misfolded amyloidogenic proteins causing the release of MOM pore forming Bax from the protective, membrane embedded Bcl-2/Bax complex. 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 (3), 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 Jonathan Gilthorpe
Experimenter: Dr Hanna Wacklin-Knecht
Local Contact: Dr Luke Clifton
Experimenter: Dr Jörgen Ådén
Experimenter: Dr Tamás Milán Nagy
Experimenter: Mrs Haiyan wang
Experimenter: Dr Sophie Ayscough

DOI: 10.5286/ISIS.E.RB2510395

ISIS Experiment Number: RB2510395

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; (2025): Apoptosis regulating Bcl-2 protein family at the mitochondrial membrane: Its function in neurodegeneration, STFC ISIS Neutron and Muon Source, https://doi.org/10.5286/ISIS.E.RB2510395

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