Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization
| Autor: | Markus Zweckstetter, Tiago F. Outeiro, Annekatrin König, Antonio Dominguez-Meijide, Alain Ibáñez de Opakua, Sergey Ryazanov, Andrei Leonov, Christian Griesinger, Maria-Sol Cima-Omori, Eftychia Vasili |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Protein aggregation therapeutic use [Benzodioxoles] Catechin 0302 clinical medicine drug therapy [Alzheimer Disease] therapeutic use [Catechin] metabolism [alpha-Synuclein] Molecular Targeted Therapy Internalization lcsh:Science Cells Cultured media_common pharmacology [Benzopyrans] Multidisciplinary biology Chemistry analogs & derivatives [Catechin] Brain Neurofibrillary Tangles Parkinson Disease 3. Good health Pharmacological interventions metabolism [Neurofibrillary Tangles] therapeutic use [Pyrazoles] alpha-Synuclein pharmacology [Catechin] metabolism [Alzheimer Disease] therapeutic use [Hydrazones] Cell biology Tau pathology media_common.quotation_subject Tau protein metabolism [Parkinson Disease] pharmacology [Benzodioxoles] tau Proteins Protein Aggregation Pathological Article pharmacology [Hydrazones] 03 medical and health sciences Protein Aggregates metabolism [Protein Aggregation Pathological] Alzheimer Disease medicine Dementia Humans Benzopyrans Benzodioxoles therapeutic use [Benzopyrans] Lewy body lcsh:R Hydrazones drug effects [Protein Aggregates] medicine.disease metabolism [Lewy Bodies] drug therapy [Parkinson Disease] metabolism [tau Proteins] 030104 developmental biology metabolism [Brain] biology.protein Pyrazoles α synuclein lcsh:Q Lewy Bodies pharmacology [Pyrazoles] Neuroscience ddc:600 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific reports 10(1), 12827 (2020). doi:10.1038/s41598-020-69744-y Scientific Reports, Vol 10, Iss 1, Pp 1-18 (2020) |
| DOI: | 10.1038/s41598-020-69744-y |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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