Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization

2020 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization​
Dominguez-Meijide, A.; Vasili, E.; König, A.; Cima-Omori, M.-S.; Ibáñez de Opakua, A.; Leonov, A.   & Ryazanov, S.  et al.​ (2020) 
Scientific Reports10(1).​ DOI: https://doi.org/10.1038/s41598-020-69744-y 

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Authors
Dominguez-Meijide, Antonio; Vasili, Eftychia; König, Annekatrin; Cima-Omori, Maria-Sol; Ibáñez de Opakua, Alain; Leonov, Andrei ; Ryazanov, Sergey ; Zweckstetter, Markus ; Griesinger, Christian ; Outeiro, Tiago F. 
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.
Issue Date
2020
Journal
Scientific Reports 
Project
EXC 2067: Multiscale Bioimaging 
Working Group
RG Griesinger 
RG Outeiro (Experimental Neurodegeneration) 
eISSN
2045-2322
Language
English

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