Research Interests:

The amyloid precursor protein (APP) is potentially involved in a variety of cellular processes, but is best known for its role as the source of a small peptide fragment known as the amyloid β peptide (Aβ). This peptide plays a major role in the development of Alzheimer’s disease in the brain. Aβ and APP are also likely involved in the pathology of another age-related human degenerative disease – inclusion body myositis – in muscle. Our lab studies the processes that generate Aβ from APP, and the factors that regulate these at the cellular and molecular level. Our aim is to use the knowledge gained from these studies to refine model systems in which to develop novel therapeutic approaches that may one day lead to effective clinical treatments for both disorders. Recent studies include the use of widely available nonsteroidal anti-inflammatories (NSAIDs, such as ibuprofen), passive immunotherapy, and lowering of cholesterol using commonly prescribed drugs.

REPRESENTATIVE PUBLICATIONS

Head E, Moffat K, Das P, Sarsoza F, Poon WW, Landsberg G, Cotman CW, Murphy MP (2005). b-Amyloid deposition and tau hyperphosphorylation in aged cats with clinical signs of dementia. Neurobiol Aging, 26 (5): 749-763.

Murphy MP, Das P, Nyborg AC, Rochette MJ, Dodson M, Loosbrock NM,  Souder TM, McLendon DC, Merit SL, Piper SC, Jansen KR, Golde TE (2003). Nicastrin overexpression increases Ab Production. FASEB J, 17: 1138-1140 (published online April 8, 2003; 10.1096/fj.02-1050fje).

Piper SC, Amtul Z, Galiñanes-Garcia L, Howard VG, Ziani-Cherif C, McLendon C, Rochette MJ, Fauq A, Golde TE, Murphy MP (2003). Peptide-based, irreversible inhibitors of g-secretase activity. Biochem Biophys Res Comm, 305: 529-533.

Rochette MJ, Murphy MP. (2002) g-Secretase: Substrates and Inhibitors. Mol Neurobiol, 26(1): 81-95.

Murphy MP, Uljon SN, Golde TE, Wang R (2002). FAD-linked PS1 mutants alter the length of Ab-like fragments derived from bAPP transmembrane domain mutants. Biochim Biophys Acta, 1586: 199-209.

Sugarman MC, Yamasaki TR, Oddo S, Echegoyen JC, Murphy MP, Golde TE, Jannatipour M, Leissring MA, LaFerla FM (2002). Inclusion body myositis-like phenotype induced by transgenic overexpression of bAPP in skeletal muscle. Proc Natl Acad Sci USA, 99(9): 6334-6339.

Ni C-Y, Murphy MP, Golde TE, Carpenter G (2001). g-Secretase-dependent cleavage and nuclear localization of the ErbB4 receptor tyrosine kinase. Science, 294: 2179-2181.

Weggen S, Eriksen J, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, Koo EH (2001). A subset of NSAIDs lower amyloidogenic Ab₄₂ independently of cyclooxygenase activity. Nature, 414: 212-216.