Journal Article: Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol
Polanco, Juan Carlos, Hand, Gabriel Rhys, Briner, Adam, Li, Chuanzhou and Götz, Jürgen (2021). Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol. Acta Neuropathologica, 141 (2), 235-256. doi: 10.1007/s00401-020-02254-3
Journal Article: Fyn kinase controls tau aggregation in vivo
Briner, Adam, Götz, Jürgen and Polanco, Juan Carlos (2020). Fyn kinase controls tau aggregation in vivo. Cell Reports, 32 (7) 108045, 108045. doi: 10.1016/j.celrep.2020.108045
Journal Article: Are you TORCing tau me? Amyloid‐β blocks the conversation between lysosomes and mitochondria
Polanco, Juan Carlos and Götz, Jürgen (2018). Are you TORCing tau me? Amyloid‐β blocks the conversation between lysosomes and mitochondria. The EMBO Journal, 37 (22) e100839, e100839. doi: 10.15252/embj.2018100839
Unravelling how exosomes induce and propagate tau pathology
(2019–2021) NHMRC Project Grant
Understanding brain connectivity associated with proteinopathy and memory impairment in Alzheimers Disease
Doctor Philosophy
Analysis of how tau spreads and forms aggregated lesions in Alzheimer¿s disease models
Doctor Philosophy
Unravelling How Exosomes Induce and Propagate Tau Pathology
Alzheimer's Disease (AD) is an irreversible and progressive dementia characterized by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid, and tau. The tau pathology in AD usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas in a pattern that suggests that neuronal interconnectivity facilitates AD progression, characterized by increasing tau aggregation and the presence of cytoplasmic neurofibrillary tangles (NFTs) in an increasing number of neurons. This suggests an active spreading mechanism, which could be via extracellular vesicles such as exosomes (Polanco et al. 2018, Nat Rev Neurol). We have established that brains from mice with tau pathology produce tau seeds 'encapsulated' within exosomes (Polanco et al. 2016, J Biol Chem). Furthermore, exosomes containing tau seeds can induce tau aggregation in recipient cells (Polanco et al. 2016, J Biol Chem; Baker, Polanco and Götz 2016, J Alzheimers Dis), and exosomes spread from neuron to neuron by hijacking endosomes (Polanco et al. 2018, Acta Neuropathol Commun). Exosomes are internalised by recipient cells via endocytosis. Consequently, tau seeds must not only be able to exit the exosomal membranes, but they must also be able to escape the endosomes in order to access cytosolic tau and induce corrupting cycles of tau aggregation. We have available projects aiming to answer questions such as:
Polanco, Juan Carlos, Hand, Gabriel Rhys, Briner, Adam, Li, Chuanzhou and Götz, Jürgen (2021). Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol. Acta Neuropathologica, 141 (2), 235-256. doi: 10.1007/s00401-020-02254-3
Fyn kinase controls tau aggregation in vivo
Briner, Adam, Götz, Jürgen and Polanco, Juan Carlos (2020). Fyn kinase controls tau aggregation in vivo. Cell Reports, 32 (7) 108045, 108045. doi: 10.1016/j.celrep.2020.108045
Are you TORCing tau me? Amyloid‐β blocks the conversation between lysosomes and mitochondria
Polanco, Juan Carlos and Götz, Jürgen (2018). Are you TORCing tau me? Amyloid‐β blocks the conversation between lysosomes and mitochondria. The EMBO Journal, 37 (22) e100839, e100839. doi: 10.15252/embj.2018100839
Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons
Polanco, Juan Carlos, Li, Chuanzhou, Durisic, Nela, Sullivan, Robert and Götz, Jürgen (2018). Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons. Acta Neuropathologica Communications, 6 (1) 10, 1-14. doi: 10.1186/s40478-018-0514-4
Amyloid-β and tau complexity - towards improved biomarkers and targeted therapies
Polanco, Juan Carlos, Li, Chuanzhou, Bodea, Liviu-Gabriel, Martinez-Marmol, Ramon, Meunier, Frederic A and Götz, Jürgen (2017). Amyloid-β and tau complexity - towards improved biomarkers and targeted therapies. Nature reviews. Neurology, 14 (1), 22-40. doi: 10.1038/nrneurol.2017.162
Polanco, Juan Carlos, Scicluna, Benjamin James, Hill, Andrew Francis and Gotz, Jurgen (2016). Extracellular vesicles isolated from the brains of rTg4510 mice seed tau protein aggregation in a threshold-dependent manner. Journal of Biological Chemistry, 291 (24), 12445-12466. doi: 10.1074/jbc.M115.709485
Baker, Sian, Polanco, Juan Carlos and Gotz, Juergen (2016). Extracellular vesicles containing P301L mutant tau accelerate pathological tau phosphorylation and oligomer formation but do not seed mature neurofibrillary tangles in ALZ17 mice. Journal of Alzheimer's Disease, 54 (3), 1207-1217. doi: 10.3233/JAD-160371
No full admission for tau to the exclusive prion club yet
Polanco, Juan Carlos and Götz, Jürgen (2015). No full admission for tau to the exclusive prion club yet. EMBO Journal, 34 (24), 2990-2992. doi: 10.15252/embj.201593311
Tau aggregation and its interplay with amyloid-β
Nisbet, Rebecca M., Polanco, Juan-Carlos, Ittner, Lars M. and Gotz, Jurgen (2014). Tau aggregation and its interplay with amyloid-β. Acta Neuropathologica, 129 (2), 207-220. doi: 10.1007/s00401-014-1371-2
Polanco, Juan Carlos, Wang, Bei, Zhou, Qi, Chy, Hun, O'Brien, Carmel and Laslett, Andrew L. (2013). Enrichment and purging of human embryonic stem cells by detection of cell surface antigens using the monoclonal antibodies TG30 and GCTM-2. Journal of Visualized Experiments (82) e50856. doi: 10.3791/50856
Polanco, Juan Carlos, Ho, Mirabelle S. H., Wang, Bei, Zhou, Qi, Wolvetang, Ernst, Mason, Elizabeth, Wells, Christine A., Kolle, Gabriel, Grimmond, Sean M., Bertoncello, Ivan, O'Brien, Carmel and Laslett, Andrew L. (2013). Identification of Unsafe Human Induced Pluripotent Stem Cell Lines Using a Robust Surrogate Assay for Pluripotency. Stem Cells, 31 (8), 1498-1510. doi: 10.1002/stem.1425
Polanco, J. C., Wilhelm, D, Davidson, T. L., Knight, D and Koopman, P (2010). Sox10 gain-of-function causes XX sex reversal in mice: implications for human 22q-linked disorders of sex development. Human Molecular Genetics, 19 (3) ddp520, 506-516. doi: 10.1093/hmg/ddp520
Arenas, Nelson Enrique, Polanco, Juan Carlos, Coronado, Sandra Milena, Durango, Clara Juliana and Gomez, Arley (2009). Design of a molecular method for subspecies specific identification of Klebsiella pneumoniae by using the 16S ribosomal subunit gene. Colombia Medica, 40 (3), 307-315.
Arenas, Nelson Enrique, Polanco, Juan Carlos, Coronado, Sandra Milena, Durango, Clara Juliana and Gomez, Arley (2009). Design of a molecular method for subspecies specific identification of Klebsiella pneumoniae by using the 16S ribosomal subunit gene. Colombia Medica, 40 (2), 194-201.
Arenas, Nelson Enrique, Gutiérrez, Andrés Julián, Salazar, Luz Mary, Polanco, Juan Carlos and Gómez, Arley (2009). Construcción de una filogenia molecular para las especies de los géneros Klebsiella y Raoultella basada en los genes ARNr 16S y ARN polimerasa subunidad. Revista Ciencias de la Salud, 7 (2), 22-29.
Functional analysis of the SRY–KRAB interaction in mouse sex determination
Polanco, Juan Carlos, Wilhelm, Dagmar, Mizusaki, Hirofumi, Jackson, Andrew, Browne, Catherine, Davidson, Tara, Harley, Vincent, Sinclair, Andrew and Koopman, Peter (2009). Functional analysis of the SRY–KRAB interaction in mouse sex determination. Biology of The Cell, 101 (1), 55-67. doi: 10.1042/BC20080061
Sry and the hesitant beginnings of male development
Polanco, Juan Carlos and Koopman, Peter (2007). Sry and the hesitant beginnings of male development. Developmental Biology, 302 (1), 13-24. doi: 10.1016/j.ydbio.2006.08.049
Plasmodium Vivax: Parasitemia Determination by Real-time Quantitative PCR in Aotus Monkeys
Polanco, Juan Carlos, Rodriguez, Josefa Antonia, Corredor, Vladimir and Patarroyo, Manuel Alfonso (2002). Plasmodium Vivax: Parasitemia Determination by Real-time Quantitative PCR in Aotus Monkeys. Experimental Parasitology, 100 (2), 131-134. doi: 10.1016/S0014-4894(02)00010-3
Plasmodium vivax: parasitemia determination by real-time quantitative PCR in Aotus monkeys
Polanco, JC, Rodriguez, JA, Corredor, V and Patarroyo, MA (2002). Plasmodium vivax: parasitemia determination by real-time quantitative PCR in Aotus monkeys. Experimental Parasitology, 100 (2), 131-134.
Possible role of KRAB-containing proteins in sex determination
Polanco, J. C., Jackson, A., Wilhelm, D. and Koopman, P. (2005). Possible role of KRAB-containing proteins in sex determination. AMSTERDAM: ELSEVIER SCIENCE BV.
Unravelling how exosomes induce and propagate tau pathology
(2019–2021) NHMRC Project Grant
Understanding brain connectivity associated with proteinopathy and memory impairment in Alzheimers Disease
Doctor Philosophy — Associate Advisor
Other advisors:
Analysis of how tau spreads and forms aggregated lesions in Alzheimer¿s disease models
Doctor Philosophy — Associate Advisor
Other advisors:
Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.
Unravelling How Exosomes Induce and Propagate Tau Pathology
Alzheimer's Disease (AD) is an irreversible and progressive dementia characterized by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid, and tau. The tau pathology in AD usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas in a pattern that suggests that neuronal interconnectivity facilitates AD progression, characterized by increasing tau aggregation and the presence of cytoplasmic neurofibrillary tangles (NFTs) in an increasing number of neurons. This suggests an active spreading mechanism, which could be via extracellular vesicles such as exosomes (Polanco et al. 2018, Nat Rev Neurol). We have established that brains from mice with tau pathology produce tau seeds 'encapsulated' within exosomes (Polanco et al. 2016, J Biol Chem). Furthermore, exosomes containing tau seeds can induce tau aggregation in recipient cells (Polanco et al. 2016, J Biol Chem; Baker, Polanco and Götz 2016, J Alzheimers Dis), and exosomes spread from neuron to neuron by hijacking endosomes (Polanco et al. 2018, Acta Neuropathol Commun). Exosomes are internalised by recipient cells via endocytosis. Consequently, tau seeds must not only be able to exit the exosomal membranes, but they must also be able to escape the endosomes in order to access cytosolic tau and induce corrupting cycles of tau aggregation. We have available projects aiming to answer questions such as: