The Taylor lab at the University of Pennsylvania is dedicated to neurodegenerative disease research. Use this site to learn about our research and the people behind the science.
Research Overview
Accumulation of misfolded and aggregated proteins is a pathological hallmark shared by many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, prion diseases, and the polyglutamine diseases. Advances in neurogenetics over the last 15 years have firmly established a role for these aberrant proteins in disease pathogenesis. In some instances, gain-of-function mutations lead to conformational changes that promote protein aggregation. In other instances, loss-of-function mutations occur in the machinery responsible for clearing defective, aggregation-prone proteins. Thus, a unifying concept has emerged regarding an underlying mechanism that contributes broadly to this class of diseases. Specifically, that certain proteins or protein fragments are vulnerable to misfolding into pathological conformations that assemble into aggregates and acquire neurotoxic properties. According to this view, when the production of such prototoxins exceeds the cell's capacity for disposing of them, neurodegeneration ensues.
This view predicts that it may be possible to develop parallel approaches to treatment based on greater insight into the normal cellular mechanisms for disposing unwanted proteins. Characterizing these mechanisms and developing target-based therapeutics are the focus of our research. Toward these ends, we have undertaken molecular and pathological analyses of cell culture and animal models of neurodegenerative diseases.
Recent Publications
McCray BA, Taylor JP. (2008) The role of autophagy in age-related neurodegeneration. Neurosignals 16(1), 75-84. Link
Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, DiProspero NA, Knight MA, Schuldiner O, Padmanabhan R, Hild M, Berry DL, Garza D, Hubbert CC, Yao T-P, Baehrecke EH, Taylor JP. (2007) HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447, 859-863. Link
Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP. (2007) Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with friedreich ataxia. Arch Neurol. 64(6):803-8.
