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Research
Dr. Nakanishi’s laboratory focuses on the role of NMDA receptor subunits in excitotoxicity and the pathogenesis of neuronal cell death.
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Biography
Dr. Nakanishi earned his Ph.D. from the University of Tokyo in 1987.
Neuroprotection by the NR3A subunit of the NMDA receptor.
Nakanishi N, Tu S, Shin Y, Cui J, Kurokawa T, Zhang D, Chen HS, Tong G, Lipton SA
J Neurosci. 2009 Apr 22;29(16):5260-5
Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.
Li H, Radford JC, Ragusa MJ, Shea KL, McKercher SR, Zaremba JD, Soussou W, Nie Z, Kang YJ, Nakanishi N, Okamoto S, Roberts AJ, Schwarz JJ, Lipton SA
Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9397-402
Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons.
Tong G, Takahashi H, Tu S, Shin Y, Talantova M, Zago W, Xia P, Nie Z, Goetz T, Zhang D, Lipton SA, Nakanishi N
J Neurophysiol. 2008 Jan;99(1):122-32
Takusan: a large gene family that regulates synaptic activity.
Tu S, Shin Y, Zago WM, States BA, Eroshkin A, Lipton SA, Tong GG, Nakanishi N
Neuron. 2007 Jul 5;55(1):69-85
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Nobuki Nakanishi's Research Focus
Alzheimer's Disease, Stroke, Autism Spectrum Disorders
Glutamate Receptors and Neurodegeneration
My laboratory focuses on the pathogenesis of neuronal cell death and a possible treatment using a gene that can regulate this process. The amino acid glutamate is the major excitatory synaptic transmitter in the brain. A class of glutamate-gated ion channels, responsive to the selective agonist N-methyl-D-aspartate (NMDA) is thought to play a crucial role in the neurotoxicity mediated by glutamate (termed excitotoxicity). Excitotoxicity, in turn, has been implicated in neuronal death in focal cerebral ischemia, epilepsy, CNS trauma, and several neurodegenerative disorders such as Huntington's disease , AIDS dementia, and Parkinsonism.
NR3A is a recently cloned glutamate-receptor subunit that shares high homology with NMDA-receptor subunits NR1 and NR2. Our data showed that NR3A protein is enriched in postsynaptic density (PSD) fractions of brain extracts from wild-type mice, and was co-immunoprecipitated with NR1 and NR2 subunits. In order to identify in vivo functions of NR3A, mutant (knock out) mice with targeted disruption of the NR3A gene have been generated in my laboratory. Whole-cell recordings with patch electrodes of acutely dissociated cortical neurons revealed that the mutant neurons exhibit larger NMDA-evoked current than wild-type cells.
Based on these data, we have proposed that NR3A is a novel regulatory subunit of NMDAR channels, and reduces NMDA-evoked current during the nomal development. We are now in the process of exploiting this unique feature of NR3A for a possible prevention of excitotoxicity by introducing this molecule as an exogenous reagent.
About Nobuki Nakanishi
Experience
Nobuki Nakanishi earned his Ph.D. from the University of Tokyo in 1987. He conducted his Ph.D. thesis research in the laboratory of Prof. Susumu Tonegawa from 1984 and 1988 at Massachusetts Institute of Technology Center for Cancer Research as a visiting scholar. From 1988-1993, he received postdoctoral training in the laboratory of Prof. Richard Axel at Columbia University, College of Physicians and Surgeons in New York as a Research Associate. Dr. Nakanishi was appointed Assistant Professor in the Department of Developmental Neurobiology at Harvard School where he conducted research from 1993-1999. He was recruited to the Sanford-Burnham Medical Research Institute in September 1999.
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