Unrevealing the multifacial role of Tau protein in the adult brain homeostasis beyond Alzheimer’s disease

While Tau protein is originally described as a mainly axonal, microtubule-associated protein, accumulating evidence supports the multiple roles of Tau in different cell processes/compartments related to synaptic signaling/plasticity (synapse) and chromatic homeostasis (nucleus). Moreover, experimental evidence demonstrates that Tau protein mediates various mechanisms through which Aβ damages the Alzheimer’s disease (AD) brain while recent studies involve Tau and its malfunction in various brain pathologies with different etiology such as epilepsy, stress-driven depression, traumatic brain injury and chronic pain. Combining in vitro, ex vivo and in vivo studies, this project aims to clarify the different functions of Tau and its malfunction or loss uncovering the converging role of Tau in different aspects of neuronal integrity and/or (mal)function in central and peripheral nervous system.

Funding Agency

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Project Reference

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Project Members

Ioannis Sotiropoulos

Principal Investigator Project Leader

Joana Margarida Silva

Assistant Researcher

João Vaz Silva

Clinician-Researcher

Patrícia Gomes

PhD Student

Romeu Alexandre Fernandes

MSc Student

Main Project Outcomes

1. Guerreiro S, Guimarães M, Silva JM, Dioli D, Vamvaka-Iakovou A, Gomes P, Megalokonomou A, Campos-Marques C, Sousa N, Leite-Almeida H, Sotiropoulos I* “Chronic pain causes 1. Tau-dependent hippocampal pathology and memory deficits” Mol Psychiatry 2022 in press.

2. Sotiropoulos I*, Trejo JL. “Brain metaplasticity” Neuroscience. 2021, 454:1-2. doi: 10.1016/j.neuroscience.2020.12.011.

3. Moosecker S, Gomes P, Dioli D, Yu S, Sotiropoulos I*, Almeida OFX * (equal contribution) “Activated PPARg Abrogates Misprocessing of Amyloid Precursor Protein, Tau Missorting and Synaptotoxicity” Front. Cell. Neurosci., 2019 https://doi.org/10.3389/fncel.2019.00239

4. Kokras N1, Sotiropoulos I1(equal contribution), Besinis D, Tzouveka E.L. Almeida O.F.X. Sousa N. Dalla C. “Neuroplasticity-related correlates of environmental enrichment combined with physical activity differ between the sexes” Europ Neuropsychopharm 2018
https://doi.org/10.1016/j.euroneuro.2018.11.1107

5. Sotiropoulos I*, Galas MC, Silva JM, Skoulakis E, Wegmann S, Maina MB, Blum D, Sayas CL, Mandelkow EM, Mandelkow E, Spillantini MG, Sousa N, Avila J, Medina M, Mudher A, Buee L. “Atypical, non-standard functions of the microtubule associated Tau protein.” Acta Neuropathol Commun. 2017, 5(1):91. doi: 10.1186/s40478-017-0489-6.

6. Wolozin B, Sotiropoulos I. “Dendritic TAU-telidge.” EBioMedicine. 2017 20:3-4. doi: 10.1016/j.ebiom.2017.05.013. Epub 2017

7. Lopes S, Lopes A, Pinto V, Guimarães MR, Sardinha MR, Duarte-Silva S, Pinheiro S, Pizarro J, Oliveira JF, Sousa N, Leite-Almeida H, Sotiropoulos I* (2016). Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits and motor impairment. Aging Cell 15(2):208-16.

8. Sotiropoulos I, Lopes A, Pinto V, Lopes S, Carlos S, Duarte-Silva S, Neves-Carvalho A, Pinto-Ribeiro F, Pinheiro S, Fernandes R, Almeida A, Sousa N, Leite-Almeida H. (2014) “Selective impact of Tau loss on nociceptive primary afferents and pain sensation” Exper Neurology 261:486-93.