Our laboratory studied the molecular mechanisms leading to normal brain aging and the pathological processes that culminate in Alzheimer’s disease and other neurodegenerative diseases by focusing on neuroprotective proteins. By comparing gene expression of young and old brains 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 mammals. We are now working to comprehensively characterize the role of Klotho in normal aging and disease. We focus on identifying the signaling pathways by which Klotho exerts its protective effects on brain cells, and also studying ways to increase Klotho expression to exploit its protective effects for therapeutic purposes.
Note: Dr. Abraham is no longer accepting new graduate students or postdocs.
Representative Publications
- Wolf EJ, Chen CD, Zhao X, Zhou Z, Morrison FG, Daskalakis NP, Stone A, Schichman S, Grenier JG, Fein-Schaffer D, Huber BR, Abraham CR, Miller MW, Logue MW. Klotho, PTSD, and advanced epigenetic age in cortical tissue. Neuropsychopharmacology. 2020 Oct 23. PMID: 33096543
- Chen CD, Li Y, Chen AK, Rudy MA, Nasse JS, Zeldich E, Polanco TJ, Abraham CR. Identification of the cleavage sites leading to the shed forms of human and mouse anti-aging and cognition-enhancing protein Klotho. PLoS One. 2020; 15(1):e0226382. PMID: 31929539
- Delitsikou V, Jarad G, Rajaram RD, Ino F, Rutkowski JM, Chen CD, Santos CXC, Scherer PE, Abraham CR, Shah AM, Feraille E, Miner JH, de Seigneux S. Klotho regulation by albuminuria is dependent on ATF3 and endoplasmic reticulum stress. FASEB J. 2020 Feb; 34(2):2087-2104. PMID: 31907991
- Zeldich E, Chen CD, Boden E, Howat B, Nasse JS, Zeldich D, Lambert AG, Yuste A, Cherry JD, Mathias RM, Ma Q, Lau NC, McKee AC, Hatzipetros T, Abraham CR. Klotho Is Neuroprotective in the Superoxide Dismutase (SOD1G93A) Mouse Model of ALS. J Mol Neurosci. 2019 Oct; 69(2):264-285. PMID: 31250273
- McGrath ER, Himali JJ, Levy D, Conner SC, Pase MP, Abraham CR, Courchesne P, Satizabal CL, Vasan RS, Beiser AS, Seshadri S. Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study. PLoS One. 2019; 14(3):e0213321. PMID: 30830941;
- Chen CD, Zeldich E, Khodr C, Camara K, Tung TY, Lauder EC, Mullen P, Polanco TJ, Liu YY, Zeldich D, Xia W, Van Nostrand WE, Brown LE, Porco JA, Abraham CR. Small Molecule Amyloid-ß Protein Precursor Processing Modulators Lower Amyloid-ß Peptide Levels via cKit Signaling. J Alzheimers Dis. 2019; 67(3):1089-1106. PMID: 30776010.
- Ikezu T, Chen C, DeLeo AM, Zeldich E, Fallin MD, Kanaan NM, Lunetta KL, Abraham CR, Logue MW, Farrer LA. Tau Phosphorylation is Impacted by Rare AKAP9 Mutations Associated with Alzheimer Disease in African Americans. J Neuroimmune Pharmacol. 2018 Jun; 13(2):254-264. PMID: 29516269.
- Robinson AA, Abraham CR, Rosene DL. Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys. Geroscience. 2018 02; 40(1):31-47. PMID: 29357021.
- Chen CD, Zeldich E, Li Y, Yuste A, Abraham CR. Activation of the Anti-Aging and Cognition-Enhancing Gene Klotho by CRISPR-dCas9 Transcriptional Effector Complex. J Mol Neurosci. 2018 Feb; 64(2):175-184.PMID: 29352444.
- Abraham CR, Mullen PC, Tucker-Zhou T, Chen CD, Zeldich E. Klotho Is a Neuroprotective and Cognition-Enhancing Protein. Vitam Horm. 2016; 101:215-38. PMID: 27125744.
Complete list can be found at BU Profiles
