TY - JOUR T1 - Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization JF - bioRxiv DO - 10.1101/2020.01.27.921643 SP - 2020.01.27.921643 AU - Antonio Dominguez-Meijide AU - Eftychia Vasili AU - Annekatrin König AU - Maria-Sol Cima-Omori AU - Andrei Leonov AU - Sergey Ryazanov AU - Markus Zweckstetter AU - Christian Griesinger AU - Tiago F. Outeiro Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/02/07/2020.01.27.921643.abstract N2 - 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. ER -