@article{dominguez-meijide_effects_2020, title = {Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization}, rights = {© 2020, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.}, url = {https://www.biorxiv.org/content/10.1101/2020.01.27.921643v2}, doi = {10.1101/2020.01.27.921643}, abstract = {{\textless}h3{\textgreater}Abstract{\textless}/h3{\textgreater} {\textless}p{\textgreater}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 Lewy bodies 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 epigallocatechin gallate decrease {aSyn} aggregation, that fulvic acid attenuates aggregation of the repeat domain of tau, 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.{\textless}/p{\textgreater}}, pages = {2020.01.27.921643}, journaltitle = {{bioRxiv}}, author = {Dominguez-Meijide, Antonio and Vasili, Eftychia and König, Annekatrin and Cima-Omori, Maria-Sol and Leonov, Andrei and Ryazanov, Sergey and Zweckstetter, Markus and Griesinger, Christian and Outeiro, Tiago F.}, urldate = {2020-04-21}, date = {2020-02-07}, langid = {english}, note = {Publisher: Cold Spring Harbor Laboratory Section: Confirmatory Results}, }