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

• Published in: Scientific reports 2020-07, Vol.10 (1), p.12827-12827, Article 12827
• Main 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.
• Format: Article
• Language: English
• Subjects: 631/378; 631/80; alpha-Synuclein - metabolism; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Benzodioxoles - pharmacology; Benzodioxoles - therapeutic use; Benzopyrans - pharmacology; Benzopyrans - therapeutic use; Brain - metabolism; Catechin - analogs & derivatives; Catechin - pharmacology; Catechin - therapeutic use; Cells, Cultured; Chemical properties; Dementia disorders; Epigallocatechin gallate; Fulvic acids; Humanities and Social Sciences; Humans; Hydrazones - pharmacology; Hydrazones - therapeutic use; Internalization; Lewy bodies; Lewy Bodies - metabolism; Molecular Targeted Therapy; Movement disorders; multidisciplinary; Neurodegenerative diseases; Neurofibrillary tangles; Neurofibrillary Tangles - metabolism; Neuromodulation; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson's disease; Pathology; Protein Aggregates - drug effects; Protein Aggregation, Pathological - metabolism; Proteins; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Science; Science (multidisciplinary); Synuclein; Tau protein; tau Proteins - metabolism; Therapeutic applications
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-69744-y

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.