Carmela Abraham, PhD

Our laboratory studies the molecular mechanisms leading to normal brain aging and the pathological processes that culminate in Alzheimer’s disease and multiple sclerosis by focusing on two neuroprotective proteins. With microarray analysis we identified genes that play crucial roles in brain dysfunction leading to cognitive decline. An example is Klotho, a cytoprotective, anti-aging protein. We found that Klotho expression is considerably decreased in the aged brains of monkeys, rats, and mice. We are now working to comprehensively characterize the role of Klotho in normal aging and disease.  Our projects are to identify the signaling pathways by which Klotho exerts its protective effects on neurons and oligodendrocytes, the myelin-producing cells.  We are also studying Klotho’s transcriptional regulation and have identified compounds to therapeutically exploit these protective effects. Another line of investigation in our lab is to understand the biology of the amyloid precursor protein (APP), the parent protein of the amyloid beta peptide (Abeta), which accumulates in the brains of Alzheimer’s disease (AD) patients and causes irreversible neurodegeneration. Certain mutations in APP result in autosomal dominant, early onset familial AD due to the increased production of Abeta. In sporadic AD, Abeta accumulates as result of inefficient clearance mechanisms. Since APP phosphorylation is involved in Abeta formation, we searched and identified molecules capable of intervening in this process to reduce the levels of toxic Abeta peptide in the brain.