Jorge J. Palop, PhD

Staff Research Investigator

Phone: (415) 734-2661
Fax: (415) 355-0824
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Assistant Professor, Department of Neurology, University of California, San Francisco  

Administrative Assistant

Amy Cheung
(415) 734-2506
amy.cheung@gladstone.ucsf.edu

More about Dr. Palop

Initially trained as a neuroanatomist and inspired by neuronal diversity and connectivity, Dr. Palop later became interested in understanding the function of neuronal networks. His research program is currently aimed at elucidating and preventing the neural processes underlying cognitive disturbances in neurological conditions, with a major focus on Alzheimer’s disease.

Dr. Palop discovered that mice genetically engineered to simulate Alzheimer’s disease display aberrant patterns of neuronal-network activity, which result
in profound anatomical and physiological alterations of learning and memory centers. Dr. Palop’s laboratory is currently investigating the molecular mechanisms leading to neuronal-network dysfunction in Alzheimer’s and is testing novel therapies to prevent cognitive decline in the disease.

Dr. Palop has received numerous competitive honors and awards, including predoctoral and postdoctoral fellowships from the Spanish Ministry
of Education and Science, the Fullbright program, the Hillblom Center for the Biology of Aging and the UCSF Memory and Aging Center. He has also been awarded with the Ramon y Cajal and the S.D. Bechtel Young Investigator Awards.

Dr. Palop has published his findings and reviews in many prestigious scientific journals, including Nature, Science, Nature Medicine, Neuron, Nature Neuroscience, PNAS and The Journal of Neuroscience. He regularly serves as a scientific reviewer for many of these journals and other organizations.

Dr. Palop earned a PhD in neuroscience (summa cum laude) from the University of Valencia, Spain. He did his postdoctoral training at UCSF and in the laboratory of Lennart Mucke, MD, at the Gladstone Institute of Neurological Disease.

 

More scientific details, please

Other Professional Titles

Assistant Professor, Department of Neurology, University of California, San Francisco 

Administrative Assistant

Amy Cheung
(415) 734-2506
amy.cheung@gladstone.ucsf.edu

Areas of Investigation

Our laboratory is interested in systems neuroscience with an emphasis on the neural basis of cognition. We are focused on understanding the neural processes that underlie cognitive decline in Alzheimer's disease (AD), and in neurological conditions associated with destabilization of neuronal networks, such as aging, epilepsy, autism, or schizophrenia. To study these complex diseases, we primarily use mouse models that recapitulate key aspects of the cognitive dysfunction and pathology of the human condition.

Numerous lines of evidence suggest that pathological levels of Aβ peptides contribute to AD pathogenesis by enhancing synaptic depression and impairing synaptic plasticity. However, its broader effects on circuits and neuronal networks are poorly understood. We discovered that aberrant patterns of neuronal network activity result in profound anatomical and physiological alterations of learning and memory centers and may contribute cognitive deficits in mouse models of AD. These unexpected findings may reflect the clinical phenotype of many pedigrees of familial AD and a significant proportion of early-onset AD patients. Therefore, we are currently investigating the molecular mechanisms of network dysfunction in AD and testing novel therapies to prevent such deficits. In this regard, we recently found that reduced voltage-gated sodium channels in fast-spiking inhibitory PV cells critically contribute to abnormalities in oscillatory brain rhythms, network synchrony, and cognitive decline in AD mice. Our findings indicate that improving the function of PV cells may be of therapeutic benefit in AD and other brain disorders associated with network instability and cognitive impairments.

Current Lab Focus

  • What are the molecular and circuit mechanisms of APP/Aβ-induced network instability?
  • Does abnormal patterns of network activity contribute to amyloid pathology and cognitive dysfunction in AD?
  • Are synaptic depression and aberrant patterns of neuronal network activity mechanistically related?
  • Is APP/Aβ part of a homeostatic mechanism controlling neuronal activity, and is it dysregulated in AD?
  • Does altered oscillatory network activity (“brain rhythms”) generated by inhibitory GABAergic interneurons play a key pathological role in AD?

Joined Gladstone

2001

Why Gladstone?

Gladstone and the extended UCSF family provide a vibrant and inspiring scientific environment where creativity, scientific rigor and a deep understanding of major biomedical challenges are essential values shared by all members of this community.   

Key Achievements

  • Discovered that transgenic models of AD have intermittent EEG epileptiform activity and nonconvulsive seizures involving cortical and hippocampal networks, which may critically alter cognitive processing. This raises the possibility that aberrant neuronal activity in AD is a primary upstream mechanism of high levels of Aβ.
  • Developed a working model of Aβ-induced cognitive dysfunction that proposes that high levels of Aβ lead to aberrant neuronal activity and compensatory inhibitory responses involving learning and memory circuits, which may critically contribute to cognitive decline in AD mouse models and possibly in humans with AD.
  • Discovered that inhibitory interneuron impairment links abnormal network activity and cognitive dysfunction in mouse models of AD. These findings suggest that improving the function of PV cells and gamma oscillatory activity may be of therapeutic benefit in AD and other brain disorders associated with network instability and cognitive impairments.

Education

University of Valencia, Spain (BSc), Biological Sciences (1994)
International University of Andalucia, Spain (MSc), Neuroscience, Summa Cum Laude (1999)
University of Valencia, Spain (PhD), Neuroscience, Summa Cum Laude (2001)

Selected Publications

  • Palop JJ, B. Jones, Kekonius L, Chin J, Yu G-Q, Raber J, Masliah E, Mucke L (2003) Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc. Natl. Acad. Sci. USA 100:9572–9577
  • Palop JJ, Chin J, Bien-Ly N, Massaro C, Yeung BZ, Yu G-Q, Mucke L (2005) Vulnerability of dentate granule cells to disruption of Arc expression in human amyloid precursor protein transgenic mice. J. Neurosci. 25:9686–9693
  • Palop JJ, Chin J, Mucke L (2006) A network dysfunction perspective on neurodegenerative diseases. Nature 443:768–773
  • Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu G-Q, Mucke L (2007) Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model. Science 316:750–754
  • Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu G-Q, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L (2007) Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55:697–711
  • Palop JJ, Mucke L (2009) Epilepsy and cognitive impairments in Alzheimer disease. Arch. Neurol. 66:435–440
  • Palop JJ, Mucke L (2010) Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nat. Neurosci. 13:812–818
  • Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, Mucke L, Palop JJ (2012) Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149:708–721
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Featured Publications

Jorge J. Palop, PhDPalop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron. 2007 Sep 6;55(5):697-711. View in: PubMed
Jorge J. Palop, PhDVerret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, Mucke L, Palop JJ. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell. 2012 Apr 27;149(3):708-21. View in: PubMed