Paul Greengard, Ph.D.

Headshot photo

Nobel Prize in Physiology and Medicine, 2000
Head of the Laboratory of Molecular and Cellular Neuroscience
Vincent Astor Professor, The Rockefeller University.

Dr. Greengard has served on the editorial boards of more than 25 journals, and advises a wide range of organizations, including the National Institutes of Health National Advisory Council on Aging, (2004–).

From the website of the Rockefeller University, Dr. Greengard writes of his current work:
"The goals of the research group are to understand more fully the molecular basis of communication between neurons in the adult mammalian brain and to elucidate the molecular defects responsible for various neurological and psychiatric disorders.

"Specifically with regard to Alzheimer’s disease, we have demonstrated that the relative amounts of APP that are converted to the nontoxic soluble form of APP (APPs) and the toxic beta-amyloid are controlled by protein phosphorylation and dephosphorylation mechanisms. Thus, activators of various protein kinases, as well as inhibitors of various protein phosphatases, reduce the amount of beta-amyloid formed by nerve cells. We are now determining the components of the signal transduction cascade that are responsible for the regulation of APP breakdown, and the formation of beta-amyloid, with the aim of developing new targets for the treatment of Alzheimer's disease."


Funded Research

Project Description Researchers Funding
Impact of APOE and Sex on Vulnerable Neuron-Specific Functional Network

APOE, the most important genetic predisposition factor for sporadic Alzheimer’s disease, long has been known for its effect on the formation of amyloid plaques. There is evidence for another role of APOE on neuron function independent of amyloid beta. We have developed tools to make the full inventory of all proteins present in a specific type of neuron, in particular in neurons that display differential vulnerability to neurodegeneration. Entorhinal cortex layer II (ECII) and hippocampal CA1 neurons are both crucial for new memory formation, and are the most susceptible to degeneration.

Discovery of CK1 Activators for Inducing the Autophagic Degradation of APP Beta-CTF

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects more than 5 million people in the United States. One of the hallmarks of AD is the accumulation of amyloid plaques in the brain of patients. The amyloid plaque is composed of beta amyloid (Abeta) peptide, which originates from an amyloid precursor protein (APP).

2015 to 2016

Uncovering Determinants of Neuronal Vulnerability in Alzheimer's Disease

Neurofibrillary tangles (NFTs) and neurodegeneration occur only in very specific regions at early stages of Alzheimer’s disease (AD), while many regions remain virtually unaffected. Using the bacTRAP technology the lab developed to isolate mRNAs from specific neuron types, we molecularly profiled these very vulnerable neurons and other neurons that are much more resistant to pathological lesions of AD. We looked for genes enriched in vulnerable neurons compared with resistant neurons, and were able to pinpoint a list of these candidate vulnerability genes.

2015 to 2016

Selective Cell Vulnerability in Alzheimer's Disease

The goal of this project is to identify cells that are both most vulnerable and most resistant to Alzheimer’s disease in order to develop drugs that will protect the most vulnerable.

Oligomer Collaborative Projects

A collaboration of members of the Research Consortium, a member of the Cure Alzheimer’s Fund Science Advisory Board and non-Cure Alzheimer’s Fund-affiliated researchers hypothesizes that an abnormal increase in levels of synaptic Abeta and, particularly, Abeta oligomers may lead to synaptic dysfunction, cognitive decline and eventually dementia. This highly innovative collaborative project will address how Abeta oligomers are formed and which types detrimentally impact synaptic dysfunction and neuronal survival in the brain.

2006 to 2008


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
William J. Netzer, Karima Bettayeb, Subhash C. Sinha, Marc Flajolet, Paul Greengard, and Victor Bustos, Gleevec shifts APP processing from a β-cleavage to a nonamyloidogenic cleavage, PNAS, 114(6), 7 Feb 2017, 1389–1394
Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, Nairn AC, Lombroso PJ, Aβ-Mediated NMDA Receptor Endocytosis in Alzheimer's Disease Involves Ubiquitination of the Tyrosine Phosphatase STEP, The Journal of Neuroscience, 30(17), Apr 28 2010, 5948-5957
Zhang Y-w, Liu Shijie, Zhang X, Li W-B, Chen Y, Huang X, Sun L, Luo W, Netzer WJ, Threadgill R, Wiegand G, Wang R, Cohen S, Greengard P, Liao F-F, Li L, Xu H, A Functional Mouse Retroposed Gene Rps23r1 Reduces Alzheimer's β-Amyloid Levels and Tau Phosphorylation, Neuron, 64(3), Nov 12, 2009, 328-40
Lagace D, Benavides D, Kansy J, Mapelli M, Greengard P, Bibb J, Eisch A, Cdk5 is essential for adult hippocampal neurogenesis, Proceedings of the National Academy of Science, Vol. 105 No. 47, October 9, 2008, 18567-18571