The Lipton laboratory studies molecular mechanisms of neurodegenerative diseases and stroke, including the role of excessive stimulation of ion channels and intracellular signaling pathways in nerve cells. Among the laboratory's accomplishments and ongoing activities are (i) the development of the first glutamate receptor/channel antagonist drug (Memantine) to be clinically approved for dementia (approved by the European Union in May, 2002 and the FDA in the USA in October, 2003), (ii) characterization of signaling events leading to neuronal injury and apoptosis in AIDS, and (iii) cloning of a gene that programs Embryonic Stem Cells to become nerve cells in the brain. These studies have led to the development of the first neuroprotective drugs to be administered successfully to humans to combat various neurodegenerative and vascular diseases of the brain.
Uehara T, Nakamura T, Yao D, Shi Z-Q, Gu Z, Masliah E, Nomura Y, Lipton SA. S-Nitrosylation of protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature 2006; 441:513-517.
Takahashi H, Shin Y, Cho S-J, Zago WM, Nakamura T, Gu Z, Ma Y, Furukawa H, Liddington RL, Zhang D, Tong G, Chen H-SV, Lipton SA. Hypoxia enhances S-nitrosylation—mediated NMDA receptor inhibition via a thiol oxygen sensor motif. Neuron 2007; 53:53-64.
Lipton SA, Li H, Zaremba JD, McKercher SR, Cui J, Kang YJ, Nie Z, Soussou W, Talantova M, Okamoto S, Nakanishi N. Autistic phenotype from MEF2C knockout cells. Science. 2009; 323:208.
Cho D-H, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, Lipton SA. S-Nitrosylation of Drp1 mediates ?-amyloid-related mitochondrial fission and neuronal injury. Science 2009; 324:102-105.