ABSTRACT
In the nervous system, cell death is important during development, replacement
of mitotic cells, and for remodeling. Cell death in response to traumatic,
ischemic, or intrinsic events can lead to loss of normal function in diseases of the
nervous system ranging from traumatic brain injury, stroke, neurodegenerative
diseases, demyelinating diseases, and cancer. The pathways toward cell death in
the nervous system have been of scientific and medical interest. During devel-
opment, there is programmed cell death that follows criteria originally described
by Lockshin and colleagues in insect cells (1) and subsequently extend into
understanding the development of the mammalian nervous system. Outside of
development, it is not clear if programmed cell death continues to play a role.
Apoptosis and necrosis were originally defined morphologically (2), and sub-
sequently, biochemical pathways for apoptosis have been intensively studied and
defined. Activation of caspases is the defining biochemical feature of apoptosis.
Apoptosis can occur in the nervous system in restricted settings, but in most
cases, cell death does not conform to the morphologic criteria of apoptosis and is
caspase independent. Autophagy, originally defined as a mechanism to recycle
organelles and proteins, has emerged as a potentially important response to
diseases involving misfolded proteins and thus may be important in certain
neurodegenerative diseases. Interference with the autophagic process can lead to
neurodegenerative phenotypes in mice (3-5).
