Discovery of Neuroprotective Agents Based on a 5-(4-Pyridinyl)-1,2,4-triazole Scaffold
Gitto, Rosaria (University of Messina. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences)
Vittorio, Serena (University of Messina. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences)
Bucolo, Federica (University of Messina. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences)
Peña Díaz, Samuel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Siracusa, Rosalba (University of Messina. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences)
Cuzzocrea, Salvatore (University of Messina. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences)
Ventura, Salvador (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Di Paola, Rosanna (University of Messina. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences)
De Luca, Laura (University of Messina. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences)

Data:	2022
Resum:	Parkinson's disease (PD) is characterized by the death of dopaminergic neurons. The common histopathological hallmark in PD patients is the formation of intracellular proteinaceous accumulations. The main constituent of these inclusions is alpha-synuclein (α-syn), an intrinsically disordered protein that in pathological conditions creates amyloid aggregates that lead to neurotoxicity and neurodegeneration. The main goal of our study was to optimize our previously identified α-syn aggregation inhibitors of 5-(4-pyridinyl)-1,2,4-triazole chemotype in terms of in vivo efficacy. Our efforts resulted in the identification of ethyl 2-((4-amino-5-(pyridin-4-yl)-4 H -1,2,4-triazol-3-yl)thio)acetate (15), which displayed the ability to prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine-induced bradykinesia as well as to affect the levels of PD markers after the administration of the same neurotoxin. In addition to the in vivo evaluation, for the 5-(4-pyridinyl)-1,2,4-triazole-based compounds, we measured the prevention of the fibrillization process using light scattering and a ThT binding assay; these compounds have been shown to slightly reduce the α-syn aggregation.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	5-(4-pyridinyl)-1,2,4-triazoles ; Synthesis ; Parkinson's disease ; Alpha synuclein ; MPTP
Publicat a:	ACS chemical neuroscience, Vol. 13, Issue 5 (March 2022) , p. 581-586, ISSN 1948-7193

DOI: 10.1021/acschemneuro.1c00849
PMID: 35179861

6 p, 6.1 MB

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