Aging, Alzheimer's disease, and brain metabolism

Isoflurane titration improves detection of hippocampal lactate by 1H-MRS. ​AK Frame, R Khazaee, M Courchesne, SK Wilson, M Bellyou,  AX Li, R Bartha, RC Cumming.  Imaging Neuroscience 2: 1–10 (2024). 

Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner. AK Frame, JL Sinka, M Courchesne, RA Muhammad, S Grahovac-Nemeth, MA Bernards, R Bartha, RC Cumming. iScience. 27(7):110342 (2024)​​

​Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies.  AK Frame, JW Robinson, NH Mahmoudzadeh, JM Tennessen , AF Simon, RC Cumming. Aging. 15(4):947-981 (2023)

Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster. DM  Long, AK Frame, PN Reardon, RC Cumming, DA Hendrix, D Kretzschmar,  JM Giebultowicz. Aging. 12(11) 10041-10058 (2020)

Aerobic glycolysis is required for spatial memory acquisition but not memory retrieval in mice. Harris RC, Lone A, Lim H, Martinez F, Frame AK, Scholl TJ, Cumming RC. eNeuro. 6(1). pii: ENEURO.0389-18 (2019)

Aerobic glycolysis in the frontal cortex correlates with memory performance in wild-type mice but not the APP/PS1 mouse model of cerebral amyloidosis.  Harris RA, Tindale L, Lone A, Singh O, Macauley SL, Stanley M, Holtzman DM, Bartha R, and Cumming RC.  Journal of Neuroscience 36(6), 1871-1878 (2016).

Age-dependent metabolic dysregulation in cancer and Alzheimer’s disease
RA Harris, L Tindale, RC Cumming
Biogerontology 15 (6), 559-577 (2014).

Reevaluating metabolism in Alzheimer's disease from the perspective of the astrocyte-neuron lactate shuttle model
JT Newington, RA Harris, RC Cumming
Journal of Neurodegenerative Diseases (2013)

​Overexpression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A in nerve cells confers resistance to amyloid β and other toxins by decreasing mitochondrial respiration and reactive oxygen species production
JT Newington, T Rappon, S Albers, DY Wong, RJ Rylett, RC Cumming
Journal of Biological Chemistry 287 (44), 37245-37258 (2012).

Beta-amyloid resistance and the Warburg effect: New insight into Alzheimer's disease from old metabolic pathways
J Newington, T Rujimethabas, R Cumming
Alzheimer's & Dementia 8 (4), P306 (2012).

Amyloid beta resistance in nerve cell lines is mediated by the Warburg effect
JT Newington, A Pitts, A Chien, R Arseneault, D Schubert, RC Cumming
PLoS One 6 (4), e19191 (2011).

​The regulation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta peptide
T Soucek, R Cumming, R Dargusch, P Maher, D Schubert
Neuron 39 (1), 43-56 (2003).

Longevity genes and metabolism

p66Shc silencing promotes aerobic glycolysis via signalling between the transcription factors NRF2 and HIF1-α
A Lone, R Khazaee, AM Kozlov, MCJ Courchesne, K Nygard , DH Betts , RC Cumming.
​Free Rad Biol Med. 241: 631-641 (2025)

p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity.
 A Lone, RA Harris, O Singh, DH Betts, RC Cumming
 Sci. Rep. 8(1):17081 (2018)

Stem cell fate and metabolism

Spatial heterogeneity of lactylation: Insights into gene expression, metabolism, and lactate transport in human embryonic stem cells 
AM Kozlov, ZCL Leung, R B Wilson, S Bhangal, K Nygard, A M Powell, NM Borradaile, DH Betts, RC Cumming. Biol Open (In Press)

p66Shc deletion confers apoptotic resistance to loss of EGFR-ERK signalling in neural stem cells.
Powell AM, Cumming RC, Betts DH.  Cell Death Dis. 16(1):479 (2025)

Deletion of p66Shc dysregulates ERK and STAT3 activity in embryonic stem cells, enhancing their naïve-like self-renewal in the presence of LIF
Powell A, Edwards NA, Hunter HLM, Kaiser P, Watson AJ, Cumming RC, Betts DH.  Stem Cells Dev. 32:15-16, 434 (2023)

Lactate preconditioning promotes a HIF-1-alpha-mediated metabolic shift from OXPHOS to glycolysis in normal human diploid fibroblasts.
AK Kozlov, A Lone, DH Betts, RC Cumming. Sci. Rep. 10:8388 (2020)
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Huntington's disease and antioxidant defence

Dithiol-based compounds maintain expression of antioxidant protein peroxiredoxin 1 that counteracts toxicity of mutant huntingtin
A Pitts, K Dailey, JT Newington, A Chien, R Arseneault, T Cann, ...
Journal of Biological Chemistry 287 (27), 22717-22729 (2012).

Protein disulfide bond formation in the cytoplasm during oxidative stress
RC Cumming, NL Andon, PA Haynes, M Park, WH Fischer, D Schubert
Journal of Biological Chemistry 279 (21), 21749-21758 (2004).
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