Cure Alzheimer's Fund Cure Alzheimer's Fund

Gopal Thinakaran, Ph.D.

Research in Dr. Thinakaran’s lab investigates mechanisms that regulate Alzheimer’s disease β-amyloid (Aβ) production and deposition. Specifically, they study the biology of BACE1 and γ-secretase, the two enzymes that sequentially cleave amyloid precursor protein (APP) to generate Aβ. Recent investigations in their lab center on the regulation of BACE1 and γ-secretase function by post-translational S-palmitoylation, live-cell analysis of dynamic membrane trafficking of BACE1, and the characterization of γ-secretase modulating protein p23. As a post-doctoral fellow, at The Johns Hopkins University School of Medicine Dr. Thinakaran participated in the early characterization of presenilin biology and investigations on how FAD mutations in PS1 affect Aβ production using cell culture and animal models. For over twelve years heI has been leading a group at the University of Chicago, investigating multiple aspects of Alzheimer’s disease cell biology including, the physiological and pathological functions of presenilins, regulation of APP trafficking and metabolism, modulation of amyloid production/deposition by post-translational modification of APP secretases and interaction with associated proteins, and the characterization of subcellular sites and membrane microdomains involved in the generation of Aβ peptides.  They have been using an integrated approach that combines hypothesis driven mutagenesis, biochemical characterization, detailed subcellular localization, advanced live cell imaging, and electrophysiology to accomplish our goals. Cultured non-neuronal cells, primary hippocampal neurons, transgenic, knock-out and gene-targeted mice serve as experimental models in the investigation.

Related Research:

BIN1 in Alzheimer’s Disease Neuropathology Gopal Thinakaran 2015-09-24 BACE1 transcytosis in Alzheimer’s disease pathogenesis Gopal Thinakaran 2012-12-06

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
BIN1 in Alzheimer’s Disease Neuropathology 2015, 2016

$300,000
BACE1 transcytosis in Alzheimer’s disease pathogenesis 2012, 2013

$200,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Rynearson, K. D., Ponnusamy, M., Prikhodko, O., … Mobley, W. C., Thinakaran, G., Tanzi, R. E., Wagner, S. L. Preclinical validation of a potent γ-secretase modulator for Alzheimer’s disease prevention, Journal of Experimental Medicine, March 2, 2021, Read More

Andrew, R. J., Fernandez, C. G., Stanley, M., Jiang, H., Nguyen, P., Rice, R. C., Buggia-Prévot, V., De Rossi, P., Vetrivel, K. S., Lamb, R., Argemi, A., Allaert, E. S., Rathbun, E. M., Krause, S. V., Wagner, S. L., Parent, A. T., Holtzman, D. M., & Thinakaran, G. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzhiemer’s disease, Proceedings of the National Academy of Sciences of the United States of America, October 23, 2017, Read More

Sadleir, K. R., Kandalepas, P. C., Buggia-Prévot, V., Nicholson, D. A., Thinakaran, G., & Vassar, R. Presynaptic dystrophic neurites surrounding amyloid plaques are sites of microtubule disruption, BACE1 elevation, and increased amyloid beta generation in Alzheimer’s disease, Acta Neuropathologica, March 18, 2016, Read More

Buggia-Prévot, V., Fernandez, C. G., Riordan, S., Vetrivel, K. S., Roseman, J., Waters, J., Bindokas, V. P., Vassar, R., & Thinakaran, G. Axonal BACE1 dynamics and targeting in hippocampal neurons: a role for Rab11 GTPase, Molecular Neurodegeneration, January 4, 2014, Read More

Buggia-Prévot, V., Fernandez, C. G., Udayar, V., Vetrivel, K. S., Elie, A., Roseman, J., Sasse, V. A., Lefkow, M., Meckler, X., Bhattacharyya, S., George, M., Kar, S., Bindokas, V. P., Parent, A. T., Rajendran, L., Band, H., Vassar, R., & Thinakaran, G. A function for EHD family proteins in unidirectional retrograde dendritic transprt of BACE1 and Alzheimer’s disease Ab production, Cell Reports, December 26, 2013, Read More

Deyts, C., Clutter, M., Pierce, N., Chakrabarty, P., Ladd, T. B., Goddi, A., Rosario, A. M., Cruz, P., Vetrivel, K., Wagner, S. L., Thinakaran, G., Golde, T. E., & Parent, A. T. APP-Mediated signaling prevents memory decline in Alzheimer’s disease mouse model, Cell Reports, April 30, 2019, Read More

Buggia-Prévot, V., & Thinakaran, G. Significance of transcytosis in Alzheimer’s disease: BACE1 takes the scenic route to axons, BioEssays, June 30, 2015, Read More

De Rossi, P., Andrew, R. J., Musial, T. F., Buggia-Prevot, V., Xu, G., Ponnusamy, M., Ly, H., Krause, S. V., Rice, R. C., de l'Estoile, V., Valin, T., Salem, S., Despa, F., Borchelt, D. R., Bindokas, V. P., Nicholson, D. A., & Thinakaran, G. Aberrant accrual of BIN1 near Alzheimer’s disease amyloid deposits in trasngenic models, Brain Pathology, December 27, 2018, Read More

Udayar, V., Buggia-Prévot, V., Guerreiro, R. L., Siegel, G., Rambabu, N., Soohoo, A. L., Ponnusamy, M., Siegenthaler, B., Bali, J., AESG, Simons, M., Ries, J., Puthenveedu, M. A., Hardy, J., Thinakaran, G., & Rajendran, L. A paired RNAi and RabGAP Overexpression screen identifies Rab11 as a regulator of beta-amyloid production, Cell Reports, December 26, 2013, Read More

De Rossi, P., Buggia-Prévot, V., Clayton, B. L., Vasquez, J. B., van Sanford, C., Andrew, R. J., Lesnick, R., Botté, A., Deyts, C., Salem, S., Rao, E., Rice, R. C., Parent, A., Kar, S., Popko, B., Pytel, P., Estus, S., & Thinakaran, G. Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and locatlization to white matter tracts, Molecular Neurodegeneration, August 3, 2016, Read More

Deyts, C., Thinakaran, G., & Parent, A. T. APP Receptor? To be or not to be, Trends in Pharmacological Sciences, January 31, 2016, Read More

De Rossi, P., Nomura, T., Andrew, R. J., Masse, N. Y., Sampathkumar, V., Musial, T. F., Sudwarts, A., Recupero, A. J., Le Metayer, T., Hansen, M. T., Shim, H. N., Krause, S. V., Freedman, D. J., Bindokas, V. P., Kasthuri, N., Nicholson, D. A., Contractor, A., & Thinakaran, G. Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation, Cell Reports, March 10, 2020, Read More

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