Linda J. Van Eldik
Title: Professor
Research area: Brain inflammation, molecular glial biology, and neurodegenerative disorders
Degree: Ph.D., Duke University, Durham, NC
Voice: 312.503.0697
Fax: 312.503.0007
e-mail:vaneldik@northwestern.edu                                                                            

Link to lab Web page:  www.vaneldiklab.com/overview.html

 

Detailed research description:
Research in the Van Eldik lab aims to elucidate the mechanisms by which chronic activation of glia in the brain, especially astrocytes and microglia, leads to damage of the neurons and progressive neurodegeneration in diseases like Alzheimer's disease. The overall goal is to utilize knowledge of potentially "druggable" pathways to develop new therapeutics. The normal role of the glia is to cooperate with the neurons to keep the brain operating smoothly. When an injury or change in the brain occurs, the glia mount an inflammation response to fight off the insult and restore the brain to its proper functioning. But in neurodegenerative diseases, the glia are over-activated, producing a state called neuroinflammation. Neuroinflammation can lead to nerve cell dysfunction or death, which is manifest as dementia. Although neuroinflammation appears to play a pivotal role in the development and progression of neurodegeneration, the molecular mechanisms underlying the process and approaches to downregulate the neuroinflammation have received little attention.

Representative publications:

Craft JM, Watterson DM, Frautschy SA and Van Eldik LJ (2004) Aminopyridazines inhibit b-amyloid induced glial activation and neuronal damage in vivo.  Neurobiol Aging 25:1283-1292.

 

Craft JM, Watterson DM, Hirsch E and Van Eldik LJ (2005) Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human beta-amyloid.  J Neuroinfl 2:15-23.

 

Ralay Ranaivo H, Craft JM, Hu W, Guo L, Wing LK, Van Eldik LJ and Watterson DM (2006) Glia as a therapeutic target: selective suppression of human Ab-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration.  J Neurosci 26:662-670.

 

Hu W, Ralay Ranaivo H, Roy SM, Behanna HA, Wing LK, Munoz L, Guo L, Van Eldik LJ and Watterson DM (2007) Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits.  Bioorg Med Chem Lett 17:414-418.

 

Somera-Molena KC, Robin B, Somera CA, Anderson C, Koh S, Behanna HA, Van Eldik LJ, Watterson DM and Wainwright MS (2007) Glial activation links early-life seizures & long-term neurologic dysfunction: evidence using a small molecule inhibitor of pro-inflammatory cytokine upregulation.  Epilepsia 48: 1785-1800.

 

Munoz L, Ralay Ranaivo H, Roy SM, Hu W, Craft JM, McNamara LK, Wing Chico L, Van Eldik LJ, and Watterson DM (2007) A novel p38a MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model. J Neuroinflammation 4: 21.

 

Thompson WL, Karpus WJ and Van Eldik LJ (2008) MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult.  J Neuroinfl 5: 35. PMID: 18706086

 

Karpus WJ, Reynolds N, Behanna HA, Van Eldik LJ and Watterson DM (2008) Inhibition of experimental autoimmune encephalomyelitis by a novel small molecular weight pro-inflammatory cytokine suppressing drug.  J Neuroimmunol 203: 73-78. PMID: 18678415

 

Fuller AD and Van Eldik LJ (2008) MFG-E8 regulates microglial phagocytosis of apoptotic neurons.  J Neuroimmune Pharmacol 3: 246-256. PMID: 18670887

 

Somera-Molina KC, Nair S, Van Eldik LJ, Watterson DM and Wainwright MS (2009) Enhanced microglial activation and proinflammatory cytokine upregulation are linked to increased susceptibility to seizures and neurologic injury in a 'two-hit' seizure model.  Brain Res 1282: 162-172. PMID: 19501063

 

Thompson WL and Van Eldik LJ (2009) Inflammatory cytokines stimulate the chemokines CCL2/MCP-1 and CCL7/MCP-3 through NFkB and MAPK dependent pathways in rat astrocytes.  Brain Res 1287: 47-57. PMID: 19577550

 

Chico LK, Van Eldik LJ and Watterson DM (2009) Targeting protein kinases in central nervous system disorders.  Nature Reviews Drug Discovery, in press. doi:10.1038/nrd2999.