Neuronal Differentiation of PC12 Cells in the Absence of Extracellular Matrix Adhesion Induces Apoptosis

Abstract

In recent years, evidence has accumulated implicating programmed cell death as a major mechanism underlying neurodegenerative processes. Programmed cell death has been described in a wide range of cell types in response to diverse factors including steroids, cytokines, ionizing radiation, virus infection, and many other agents¹. It is an active process that is often dependent on RNA and protein synthesis and probably involves a number of complex pathways that ultimately result in endonuclease activation, DNA fragmentation, and cell death. Programmed cell death may be distinguished form “accidental” cell death that results from hypoxia, trauma, or toxic agents, although all of these processes may involve common pathways². In the brain, programmed cell death has been well established as a part of normal development³, following excitotoxic death of targets of innervation⁴, and as a consequence of amyloid toxicity^5,6. These findings suggest that programmed cell death may be a central common pathway in numerous neurodenegerative processes including Alzheimer’s disease. This concept is supported by observations that neurons are strictly dependent on growth factors to prevent programmed cell death and promote survival⁷ and by evidence that growth factor response mechanisms are attenuated in aging⁸.