Posted January 7, 2015
Kalipada Pahan, Ph.D., Rush University Medical Center

Kalipada Pahan, Ph.D. Currently, there are no effective therapies available to treat Alzheimer's disease despite intensive investigations. Although it is still unclear what causes Alzheimer's, researchers have identified a wide number of potential biological and lifestyle risk factors that contribute to the onset of the disease. The Peer Reviewed Alzheimer's Disease Research Program (PRARP) is investigating how well-known Alzheimer's disease risk factors, when combined with traumatic brain injuries, produce long-term neurodegeneration. Dr. Kalipada Pahan, the Floyd A. Davis Professor of Neurology at the Rush University Medical Center has been carefully studying the mechanisms of neuro-inflammation in Alzheimer's disease. Dr. Pahan believes that neuro-inflammation is a significant contributor to neurodegeneration caused by both Alzheimer's disease and traumatic brain injuries.

"Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Alzheimer's disease," said Kalipada Pahan, PhD. In an effort to develop novel therapeutic targets to treat Alzheimer's disease, Dr. Pahan received funding in 2011 from the PRARP to study the mechanisms of microglial activation in Alzheimer's disease. Normally, microglial cells secrete hormone-like compounds that promote neuron (nerve cell) survival. In Alzheimer's disease, hyper-activation of the microglial cells results in neuro-inflammation and subsequent damage to the neurons. Microglial cells are activated by a protein fragment known as beta-amyloid, the main component of the amyloid plaques commonly found in the brains of Alzheimer's patients. Dr. Pahan and others believe beta-amyloid may play a significant role in neuro-inflammation. Therefore, the plaques may be exacerbating the neuro-inflammatory response of the microglial cells.

The nuclear factor kappa B (NF-κB) transcription factor is an important regulator of neuro-inflammation. Dr. Pahan and his team hypothesized that peptides which block specific binding domains important in NF-κB activation would modulate neuro-inflammatory cascades and block further damage to the neurons. "After intranasal administration, the peptide enters into the brain, inhibits microglial activation, protects neurons, and improves memory and learning in mice with AD-like pathology", said Dr. Pahan. Using animal modeling, treatment with the peptide improved cognitive function in animals predisposed to Alzheimer's disease. In a separate study, Dr. Pahan showed that increased activation of NF-κB in the cortex and hippocampus of Alzheimer's patients negatively affects cognitive function. Therefore, it is conceivable that these peptides may help Alzheimer's patients maintain or recover lost cognitive function.

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