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August 2020
Antioxidants
Menezes R, Foito A, Jardim C, Costa I, Garcia G, Rosado-Ramos R, Freitag S, Alexander CJ, Outeiro TF, Stewart D, Santos CN
August 2020
Journal of Physical Chemistry Letters
Ghosh S, Oleksiievets N, Enderlein J, Chizhik AI
August 2020
Elife
Eckermann M, Frohn J, Reichardt M, Osterhoff M, Sprung M, Westermeier F, Tzankov A, Werlein C, Kuehnel M, Jonigk D, Salditt T
August 2020
Proceedings of the National Academy of Sciences
Pape JK, Stephan T, Balzarotti F, Büchner R, Lange F, Riedel D, Jakobs S, Hell SW
August 2020
International Journal of Molecular Sciences
Morato Torres CA, Wassouf Z, Zafar F, Sastre D, Outeiro TF, Schüle B
August 2020
PLoS Computational Biology
Salfer M, Collado JF, Baumeister W, Fernández-Busnadiego R, Martínez-Sánchez A
August 2020
bioRxiv
Trinkaus VA, Riera-Tur I, Martínez-Sánchez A, Bäuerlein FJB, Guo Q, Arzberger T, Baumeister W, Dudanova I, Hipp MS, Hartl FU, Fernández-Busnadiego R
August 2020
Brain Pathology
Koss DJ, Bondarevaite O, Adams S, Leite M, Giorgini F, Attems J, Outeiro TF
July 2020
Scientific Reports
Dominguez-Meijide A, Vasili E, König A, Cima-Omori MS, Ibáñez de Opakua A, Leonov A, Ryazanov S, Zweckstetter M, Griesinger C, Outeiro TF

Authors

Dominguez-Meijide A, Vasili E, König A, Cima-Omori MS, Ibáñez de Opakua A, Leonov A, Ryazanov S, Zweckstetter M, Griesinger C, Outeiro TF

Journal

Scientific Reports

Citation

Sci Rep 10, 12827 (2020).

Abstract

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative disorders of the elderly and, therefore, affect a growing number of patients worldwide. Both diseases share, as a common hallmark, the accumulation of characteristic protein aggregates, known as Lewy bodies (LB) in PD, and neurofibrillary tangles in AD. LBs are primarily composed of misfolded α-synuclein (aSyn), and neurofibrillary tangles are primarily composed of tau protein. Importantly, upon pathological evaluation, most AD and PD/Lewy body dementia cases exhibit mixed pathology, with the co-occurrence of both LB and neurofibrillary tangles, among other protein inclusions. Recent studies suggest that both aSyn and tau pathology can spread and propagate through neuronal connections. Therefore, it is important to investigate the mechanisms underlying aggregation and propagation of these proteins for the development of novel therapeutic strategies. Here, we assessed the effects of different pharmacological interventions on the aggregation and internalization of tau and aSyn. We found that anle138b and fulvic acid decrease aSyn and tau aggregation, that epigallocatechin gallate decreases aSyn aggregation, and that dynasore reduces tau internalization. Establishing the effects of small molecules with different chemical properties on the aggregation and spreading of aSyn and tau will be important for the development of future therapeutic interventions.

DOI

10.1038/s41598-020-69744-y

 
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