Jorge Palop’s lab aims to understand the neural processes underlying cognitive decline in Alzheimer's disease and neurological conditions, such as epilepsy, autism, and schizophrenia. His team focuses on a type of neuron that stabilizes neuronal networks in the brain, called inhibitory interneurons, and the role they may play in the cognitive dysfunction and abnormal patterns of neuronal network activity that accompany Alzheimer’s disease. Ultimately, Palop’s group aims to define the mechanisms of cognitive dysfunction at the molecular, circuit, and network level, as well as to develop novel therapeutic approaches to restore brain functions in Alzheimer’s disease.
Disease Areas
Areas of Expertise
Lab Focus
Research Impact
Palop discovered that mice genetically engineered to simulate Alzheimer's disease (by producing excess beta-amyloid protein) develop aberrant patterns of neuronal network activity, including abnormal synchronisation and seizures. These patterns resemble the epileptic symptoms observed in many patients with early-onset familial Alzheimer’s disease, the hyperactivation of neuronal networks detected in patients with sporadic Alzheimer’s disease, and in non-demented people who carry amyloid deposits.
Palop and his team found that in Alzheimer’s mouse models, these symptoms could be attributed to the alteration of inhibitory interneurons. Importantly, they showed that by supplying genetically modified interneurons in the brain of Alzheimer’s mice, or by chemically enhancing the function of resident interneurons, they could restore the cognitive functions and brain oscillatory rhythms in these mice. The findings pave the way for therapeutic interventions targeting the function of inhibitory interneurons, which the lab is currently pursuing through a combination of cell-based and pharmacological approaches.
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Professional Titles
Associate Investigator, Gladstone Institutes
Associate Professor of Neurology, UC San Francisco
Bio
Jorge J. Palop is an associate investigator at the Gladstone Institutes. He is also an associate professor of neurology at UC San Francisco (UCSF).
Palop has received numerous competitive honors and awards, including predoctoral and postdoctoral fellowships from the Spanish Ministry of Education and Science, the Fulbright program, the Hillblom Center for the Biology of Aging, and the Memory and Aging Center at UCSF, as well as the Ramon y Cajal and the S.D. Bechtel Young Investigator Awards. He has published his findings and reviews in many prestigious scientific journals, including Cell, 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. He is a reviewing editor of eNeuro, the open-access online journal of the Society of Neuroscience. 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 at Gladstone.
Why Are You Dedicated to Discovery?
“I’m fascinated by the biological processes that underlie cognition; I think that understanding those processes at the cellular and network level will lead to real breakthroughs in how we treat cognitive decline in neurological diseases.”
Honors and Awards
2016 UCSF Neuroscience Graduate Program, UC San Francisco
2016 UCSF Biomedical Sciences Graduate Program, UC San Francisco
2015 Keynote speaker, 1st National Hispanic Alzheimer’s Conference, San Antonio
2014 Reviewing Editor, eNeuro
2014 New Investigator R01, National Institute of Aging (NIH)
2013 Early Career Review program for the National Institutes of Health
2013 Investigator Initiated Research Grant, Alzheimer’s Association
2008 Ramón y Cajal Investigator Award, the Spanish Science and Education Ministry
2008 S.D. Bechtel Young Investigator Award
2006 McBean Postdoctoral Fellowship, Memory and Aging Center, UC San Francisco
2003 C. Lester and Audrey Hogan Fellowship Award
2003 Postdoctoral Fellowship, Hillblom Center for the Biology of Aging, UC San Francisco
2001 Postdoctoral Fellowship, Spanish Science and Education Ministry
2001 Fulbright Postdoctoral Fellowship
1997 Master Fellowship of the International University of Andalucia, Spain
1996 Predoctoral Fellowship, Spanish Science and Education Ministry
Publications
- Microglial Gi-dependent dynamics regulate brain network hyperexcitability. Merlini M, Rafalski VA, Ma K, Kim KY, Bushong EA, Rios Coronado PE, Yan Z, Mendiola AS, Sozmen EG, Ryu JK, Haberl MG, Madany M, Sampson DN, Petersen MA, Bardehle S, Tognatta R, Dean T, Acevedo RM, Cabriga B, Thomas R, Coughlin SR, Ellisman MH, Palop JJ, Akassoglou K. Nat Neurosci. 2020 Dec 14.
- Behavioral and neural network abnormalities in human APP transgenic mice resemble those of App knock-in mice and are modulated by familial Alzheimer's disease mutations but not by inhibition of BACE1. Johnson ECB, Ho K, Yu GQ, Das M, Sanchez PE, Djukic B, Lopez I, Yu X, Gill M, Zhang W, Paz JT, Palop JJ, Mucke L. Mol Neurodegener. 2020 09 14; 15(1):53.
- A second X chromosome contributes to resilience in a mouse model of Alzheimer's disease. Davis EJ, Broestl L, Abdulai-Saiku S, Worden K, Bonham LW, Miñones-Moyano E, Moreno AJ, Wang D, Chang K, Williams G, Garay BI, Lobach I, Devidze N, Kim D, Anderson-Bergman C, Yu GQ, White CC, Harris JA, Miller BL, Bennett DA, Arnold AP, De Jager PL, Palop JJ, Panning B, Yokoyama JS, Mucke L, Dubal DB. Sci Transl Med. 2020 Aug 26; 12(558).
- GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models. Hanson JE, Ma K, Elstrott J, Weber M, Saillet S, Khan AS, Simms J, Liu B, Kim TA, Yu GQ, Chen Y, Wang TM, Jiang Z, Liederer BM, Deshmukh G, Solanoy H, Chan C, Sellers BD, Volgraf M, Schwarz JB, Hackos DH, Weimer RM, Sheng M, Gill TM, Scearce-Levie K, Palop JJ. Cell Rep. 2020 01 14; 30(2):381-396.e4.
- What electrophysiology tells us about Alzheimer's disease: a window into the synchronization and connectivity of brain neurons. Babiloni C, Blinowska K, Bonanni L, Cichocki A, De Haan W, Del Percio C, Dubois B, Escudero J, Fernández A, Frisoni G, Guntekin B, Hajos M, Hampel H, Ifeachor E, Kilborn K, Kumar S, Johnsen K, Johannsson M, Jeong J, LeBeau F, Lizio R, Lopes da Silva F, Maestú F, McGeown WJ, McKeith I, Moretti DV, Nobili F, Olichney J, Onofrj M, Palop JJ, Rowan M, Stocchi F, Struzik ZM, Tanila H, Teipel S, Taylor JP, Weiergräber M, Yener G, Young-Pearse T, Drinkenburg WH, Randall F. Neurobiol Aging. 2020 01; 85:58-73.
- Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice. Broestl L, Worden K, Moreno AJ, Davis EJ, Wang D, Garay B, Singh T, Verret L, Palop JJ, Dubal DB. eNeuro. 2018 Nov-Dec; 5(6).
- Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer's Disease. Martinez-Losa M, Tracy TE, Ma K, Verret L, Clemente-Perez A, Khan AS, Cobos I, Ho K, Gan L, Mucke L, Alvarez-Dolado M, Palop JJ. Neuron. 2018 04 04; 98(1):75-89.e5.
- Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research? Scharfman HE, Kanner AM, Friedman A, Blümcke I, Crocker CE, Cendes F, Diaz-Arrastia R, Förstl H, Fenton AA, Grace AA, Palop J, Morrison J, Nehlig A, Prasad A, Wilcox KS, Jette N, Pohlmann-Eden B. Epilepsy Behav. 2018 01; 78:302-312.
- Ketogenic diet or BHB improves epileptiform spikes, memory, survival in Alzheimer's model Newman JC , Kroll F , Ulrich S, Palop JJ, Verdin E. . bioRxiv, 136226. 2017.
- Network abnormalities and interneuron dysfunction in Alzheimer disease. Palop JJ, Mucke L. Nat Rev Neurosci. 2016 12; 17(12):777-792.
- Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-ß signaling and astrocyte functions. Schachtrup C, Ryu JK, Mammadzada K, Khan AS, Carlton PM, Perez A, Christian F, Le Moan N, Vagena E, Baeza-Raja B, Rafalski V, Chan JP, Nitschke R, Houslay MD, Ellisman MH, Wyss-Coray T, Palop JJ, Akassoglou K. Nat Neurosci. 2015 Aug; 18(8):1077-80.
- Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model. Heng MY, Lin ST, Verret L, Huang Y, Kamiya S, Padiath QS, Tong Y, Palop JJ, Huang EJ, Ptácek LJ, Fu YH. J Clin Invest. 2013 Jun; 123(6):2719-29.
- Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Ho K, Yu GQ, Palop JJ, Mucke L. Proc Natl Acad Sci U S A. 2012 Oct 16; 109(42):E2895-903.
- Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, Mucke L, Palop JJ. Cell. 2012 Apr 27; 149(3):708-21.
- Amyloid-ß/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. Roberson ED, Halabisky B, Yoo JW, Yao J, Chin J, Yan F, Wu T, Hamto P, Devidze N, Yu GQ, Palop JJ, Noebels JL, Mucke L. J Neurosci. 2011 Jan 12; 31(2):700-11.
- Quantifying biomarkers of cognitive dysfunction and neuronal network hyperexcitability in mouse models of Alzheimer's disease: depletion of calcium-dependent proteins and inhibitory hippocampal remodeling. Palop JJ, Mucke L, Roberson ED. Methods Mol Biol. 2011; 670:245-62.
- Step-by-step in situ hybridization method for localizing gene expression changes in the brain. Palop JJ, Roberson ED, Cobos I. Methods Mol Biol. 2011; 670:207-30.
- Transsynaptic progression of amyloid-ß-induced neuronal dysfunction within the entorhinal-hippocampal network. Harris JA, Devidze N, Verret L, Ho K, Halabisky B, Thwin MT, Kim D, Hamto P, Lo I, Yu GQ, Palop JJ, Masliah E, Mucke L. Neuron. 2010 Nov 04; 68(3):428-41.
- Arc regulates spine morphology and maintains network stability in vivo. Peebles CL, Yoo J, Thwin MT, Palop JJ, Noebels JL, Finkbeiner S. Proc Natl Acad Sci U S A. 2010 Oct 19; 107(42):18173-8.
- Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Palop JJ, Mucke L. Nat Neurosci. 2010 Jul; 13(7):812-8.
- Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice. Buttini M, Masliah E, Yu GQ, Palop JJ, Chang S, Bernardo A, Lin C, Wyss-Coray T, Huang Y, Mucke L. Am J Pathol. 2010 Aug; 177(2):563-9.
- Distinct roles of GABAergic interneurons in the regulation of striatal output pathways. Gittis AH, Nelson AB, Thwin MT, Palop JJ, Kreitzer AC. J Neurosci. 2010 Feb 10; 30(6):2223-34.
- Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Sun B, Halabisky B, Zhou Y, Palop JJ, Yu G, Mucke L, Gan L. Cell Stem Cell. 2009 Dec 04; 5(6):624-33.
- Synaptic depression and aberrant excitatory network activity in Alzheimer's disease: two faces of the same coin? Palop JJ, Mucke L. Neuromolecular Med. 2010 Mar; 12(1):48-55.
- Epilepsy and cognitive impairments in Alzheimer disease. Palop JJ, Mucke L. Arch Neurol. 2009 Apr; 66(4):435-40.
- Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Sanchez-Mejia RO, Newman JW, Toh S, Yu GQ, Zhou Y, Halabisky B, Cissé M, Scearce-Levie K, Cheng IH, Gan L, Palop JJ, Bonventre JV, Mucke L. Nat Neurosci. 2008 Nov; 11(11):1311-8.
- Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer's disease. Meilandt WJ, Yu GQ, Chin J, Roberson ED, Palop JJ, Wu T, Scearce-Levie K, Mucke L. J Neurosci. 2008 May 07; 28(19):5007-17.
- Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Palop 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. Neuron. 2007 Sep 06; 55(5):697-711.
- Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H, Bien-Ly N, Puoliväli J, Lesné S, Ashe KH, Muchowski PJ, Mucke L. J Biol Chem. 2007 Aug 17; 282(33):23818-28.
- Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L. Science. 2007 May 04; 316(5825):750-4.
- Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's disease. Chin J, Massaro CM, Palop JJ, Thwin MT, Yu GQ, Bien-Ly N, Bender A, Mucke L. J Neurosci. 2007 Mar 14; 27(11):2727-33.
- Altered navigational strategy use and visuospatial deficits in hAPP transgenic mice. Deipolyi AR, Fang S, Palop JJ, Yu GQ, Wang X, Mucke L. Neurobiol Aging. 2008 Feb; 29(2):253-66.
- A network dysfunction perspective on neurodegenerative diseases. Palop JJ, Chin J, Mucke L. Nature. 2006 Oct 19; 443(7113):768-73.
- Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. Chin J, Palop JJ, Puoliväli J, Massaro C, Bien-Ly N, Gerstein H, Scearce-Levie K, Masliah E, Mucke L. J Neurosci. 2005 Oct 19; 25(42):9694-703.
- Vulnerability of dentate granule cells to disruption of arc expression in human amyloid precursor protein transgenic mice. Palop JJ, Chin J, Bien-Ly N, Massaro C, Yeung BZ, Yu GQ, Mucke L. J Neurosci. 2005 Oct 19; 25(42):9686-93.
- Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Cheng IH, Palop JJ, Esposito LA, Bien-Ly N, Yan F, Mucke L. Nat Med. 2004 Nov; 10(11):1190-2.
- Fyn kinase modulates synaptotoxicity, but not aberrant sprouting, in human amyloid precursor protein transgenic mice. Chin J, Palop JJ, Yu GQ, Kojima N, Masliah E, Mucke L. J Neurosci. 2004 May 12; 24(19):4692-7.
- Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Palop JJ, Jones B, Kekonius L, Chin J, Yu GQ, Raber J, Masliah E, Mucke L. Proc Natl Acad Sci U S A. 2003 Aug 05; 100(16):9572-7.
- Cytochemical techniques for zinc and heavy metals localization in nerve cells. López-García C, Varea E, Palop JJ, Nacher J, Ramirez C, Ponsoda X, Molowny A. Microsc Res Tech. 2002 Mar 01; 56(5):318-31.
- Early histological maturation in the hippocampus of the guinea pig. Nacher J, Palop JJ, Ramirez C, Molowny A, Lopez-Garcia C. Brain Behav Evol. 2000 Jun; 56(1):38-44.
- Microglial cells during the lesion-regeneration of the lizard medial cortex. Nacher J, Ramírez C, Palop JJ, Artal P, Molowny A, López-García C. Histol Histopathol. 1999 01; 14(1):103-17.
- Radial glia and cell debris removal during lesion-regeneration of the lizard medial cortex. Nacher J, Ramírez C, Palop JJ, Molowny A, Luis de la Iglesia JA, López-García C. Histol Histopathol. 1999 01; 14(1):89-101.
- Zinc-positive presynaptic boutons of the rabbit hippocampus during early postnatal development. Sanchez-Andres JV, Palop JJ, Ramirez C, Nacher J, Molowny A, Lopez-Gracia C. Brain Res Dev Brain Res. 1997 Nov 12; 103(2):171-83.
Contact
Jorge Palop
415.734.2661
Theodora Pak
Administrative Assistant III
415.734.2513