"Ferroptosis: a regulated mode of cell death involved in diverse human diseases"

Richard has made some substantial advances in our understanding of how growth factors and nutrients combine to control cell growth and other processes. I think his new work on Ferroptosis also looks very important – I’ll paste his abstract below as well as a link to most of his other publications. I hope many of you will be able to come along.

https://www.ncbi.nlm.nih.gov/pubmed/?term=lamb+rf
Ferroptosis, a regulated iron-dependent form of cell death, is implicated in an increasing variety of human diseases, including ischemic organ injury and neuropathies [1] [2]. Accumulation of oxidized phospholipids [3] is a key feature of cell death by ferroptosis, with polyunsaturated fatty acids (PUFAs) the preferred substrates for oxidation [1, 4, 5]. Ferroptosis research has focused hitherto on identifying iron-dependant mechanisms that trigger lipid oxidation [1, 6, 7] or understanding how membrane properties are altered by lipid oxidation to induce cell death [8, 9]. Our investigations developed by asking how common cancer-causing mutations impacted on cell viability under nutrient-deprived conditions and identified mediators of sensitivity to ferroptosis following deprivation of cystine [10]. We also identified a novel phenomenon: a cell-cell spread of ferroptosis that occurs in normal epithelial monolayers under oxidative stress, and will describe unpublished work on identifying how ferroptosis is triggered and spread from cell to cell.
PUFAs are known to be highly enriched in neurons [11] and oxidative stress resulting in ferroptosis has recently been strongly implicated in neuronal cell death in Alzheimers [12, 13], Huntingtons [14-16], Parkinsons [17-19] and amyotrophic lateral sclerosis (ALS [20-22]) diseases. The two FDA-approved drugs currently used in ALS patients are thought to act either by inhibiting glutamate neurotoxicity (Riluzole [23]) or by quenching lipid peroxidation (Edaravone [24, 25]). Both processes are now known to occur either via [26] or during [3] ferroptosis. Interestingly, cell-cell neuronal spread may also underlie disease progression in ALS [27, 28], although the mechanism of spread is unknown. I will describe recent unpublished work where we have found that motor neurons (MNs) derived from mSOD1 G93A mice, which develop many of the symptoms of human ALS, are preferentially sensitive to ferroptosis.

REFERENCES

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