Role of cell cycle proteins in CNS injury.
Following trauma or ischemia to the central nervous system (CNS), there is a marked increase in the expression of cell cycle-related proteins. This up-regulation is associated with apoptosis of post-mitotic cells, including neurons and oligodendrocytes, both in vitro and in vivo. Cell cycle activation also induces proliferation of astrocytes and microglia, contributing to the glial scar and microglial activation with release of inflammatory factors. Treatment with cell cycle inhibitors in CNS injury models inhibits glial scar formation and neuronal cell death, resulting in substantially decreased lesion volumes and improved behavioral recovery. Here we critically review the role of cell cycle pathways in the pathophysiology of experimental stroke, traumatic brain injury and spinal cord injury, and discuss the potential of cell cycle inhibitors as neuroprotective agents.
Byrnes
Kimberly R
KR
Department of Neuroscience, Georgetown University Medical Center, Room EP16A, New Research Building, 3970 Reservoir Rd., NW, Washington, DC 20057, USA. krb27@georgetown.edu
Faden
Alan I
AI
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D002490:Central Nervous System / Q000293:injuries* / Q000503:physiopathology*; D002493:Central Nervous System Diseases / Q000503:physiopathology*; D006801:Humans; D017628:Microglia / Q000187:drug effects; D018696:Neuroprotective Agents
D018797:Cell Cycle Proteins; D018696:Neuroprotective Agents