RT Journal Article
SR Electronic
T1 Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.27.921643
DO 10.1101/2020.01.27.921643
A1 Antonio Dominguez-Meijide
A1 Eftychia Vasili
A1 Annekatrin König
A1 Maria-Sol Cima-Omori
A1 Andrei Leonov
A1 Sergey Ryazanov
A1 Markus Zweckstetter
A1 Christian Griesinger
A1 Tiago F. Outeiro
YR 2020
UL http://biorxiv.org/content/early/2020/02/07/2020.01.27.921643.abstract
AB 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.