Neuronal Cell Death

Abstract

Neuronal cell death occurs extensively during development and pathology, where it is especially important because of the limited capacity of adult neurons to proliferate or be replaced. The concept of cell death used to be simple as there were just two or three types, so we just had to work out which type was involved in our particular pathology and then block it. However, we now know that there are at least a dozen ways for neurons to die, that blocking a particular mechanism of cell death may not prevent the cell from dying, and that non-neuronal cells also contribute to neuronal death. We review here the mechanisms of neuronal death by intrinsic and extrinsic apoptosis, oncosis, necroptosis, parthanatos, ferroptosis, sarmoptosis, autophagic cell death, autosis, autolysis, paraptosis, pyroptosis, phagoptosis, and mitochondrial permeability transition. We next explore the mechanisms of neuronal death during development, and those induced by axotomy, aberrant cell-cycle reentry, glutamate (excitoxicity and oxytosis), loss of connected neurons, aggregated proteins and the unfolded protein response, oxidants, inflammation, and microglia. We then reassess which forms of cell death occur in stroke and Alzheimer's disease, two of the most important pathologies involving neuronal cell death. We also discuss why it has been so difficult to pinpoint the type of neuronal death involved, if and why the mechanism of neuronal death matters, the molecular overlap and interplay between death subroutines, and the therapeutic implications of these multiple overlapping forms of neuronal death.

Quantitative Structure–Cytotoxicity Relationship of Pyrano[4,3-b]chromones

“…This suggests that there may be no connection between the tumor specificity and apoptosis-inducing activity. There are a variety of types of cell death reported (15). Further study is needed to determine which type of cell death 16 induces in human OSCC cell lines.…”

Quantitative Structure–Cytotoxicity Relationship of 3-(N-Cyclicamino)chromone Derivatives

“…These results suggest that these structural isomers, 2-(N-cyclicamino)chromones and 3-(N-cyclicamino)chromones, have no apoptosis-inducing activity, despite exhibiting different modes of growth inhibition (either cytotoxic or cytostatic). There are a variety of types of cell death reported (20). Further study is needed to determine which type of cell death 3a induces in human OSCC cell lines.…”

“…When HSC-2 cells were incubated for 24 h with increasing concentrations (20,40,80 or 160 μM) of 3a, cells became gradually enlarged (upper column in Figure 3A). In contrast, actinomycin D treatment induced cell shrinkage, characteristic of apoptosis ( Figure 3A).…”

Quantitative Structure–Cytotoxicity Relationship of 2-(N-cyclicamino)chromone Derivatives

“…We chose descriptors that show significant correlation with each of T, N, and T-N in both analyses (Table II). Among a total of 3089 descriptors, 13 descriptors correlated well with cytotoxicity and tumor specificity (Table III) and mitochondrial permeability transition (20). Further study is needed regarding which type of cell death 5c induces in human OSCC cell lines.…”

“…When HSC-2 cells were incubated for 24 h with increasing concentrations (20,40,80 or 160 μM) of 5c, cells became gradually enlarged (upper column in Figure 3). Cell enlargement and damage were more pronounced when incubation time was prolonged to 48 h (lower column in Figure 3).…”