…
comment: The repository administrator has not yet configured an RDF license.
primary topic: Sulfamerazine as a potential modulator against α-synuclein aggregation and associated toxicity

Sulfamerazine as a potential modulator against α-synuclein aggregation and associated toxicity
type: AcademicArticle
type: Article
abstract: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. The presence of Lewy bodies, primarily consisting of amyloid aggregates of the protein α-synuclein (α-Syn), is a common feature seen in dopaminergic neurons in (PD) patients. In the present study, we screened 2320 FDA-approved drugs and found 3 lead molecules, sulfamerazine, lathosterol, and tamoxifen, that reproducibly inhibited α-Syn fibrillation. Dose-response studies showed that sulfamerazine and lathosterol are relatively more potent than tamoxifen in inhibiting α-Syn aggregation. Among the lead compounds, sulfamerazine showed a significant reduction in α-Syn aggregation and associated toxicity in Caenorhabditis elegans model of PD. Sulfamerazine also reduced the accumulation of α-Syn aggregates in neuronal SH-SY5Y cells. Microscale thermophoresis confirmed the binding of sulfamerazine to α-Syn. NMR studies corroborated the binding of sulfamerazine with α-Syn and show that upon interaction, α-Syn is sequestered into large soluble dispersed assemblies, which is similar to as seen in transmission electron microscopy. We conclude that sulfamerazine and its derivatives hold promise as therapeutic agents against Parkinson's disease.
date: 2025-03
volume: 16
issue: 5
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

ACS Chem. Neurosci.
type: Collection

Ashutosh Kumar
type: Person
given name: Ashutosh
family name: Kumar

Arpit Tyagi
type: Person
given name: Arpit
family name: Tyagi

Nagesh Y Kadam
type: Person
given name: Nagesh Y
family name: Kadam

Rajlaxmi Panigrahi
type: Person
given name: Rajlaxmi
family name: Panigrahi

Prashant Singh
type: Person
given name: Prashant
family name: Singh

Daniel E Otzen
type: Person
given name: Daniel E
family name: Otzen

Abhishek Sharma
type: Person
given name: Abhishek
family name: Sharma

Arpit Mehrotra
type: Person
given name: Arpit
family name: Mehrotra

Giulia Kleijwegt
type: Person
given name: Giulia
family name: Kleijwegt

Madhumita Dey
type: Person
given name: Madhumita
family name: Dey

Janni Nielsen
type: Person
given name: Janni
family name: Nielsen

Priyanka Singh
type: Person
given name: Priyanka
family name: Singh

Muhammad Aquib
type: Person
given name: Muhammad
family name: Aquib

Alka Rao
type: Person
given name: Alka
family name: Rao

Deepak Sharma
type: Person
given name: Deepak
family name: Sharma

Krishna Upadhayay
type: Person
given name: Krishna
family name: Upadhayay

HTML Summary of #3272 Sulfamerazine as a potential modulator against α-synuclein aggregation and associated toxicity
format: text/html
primary topic: Sulfamerazine as a potential modulator against α-synuclein aggregation and associated toxicity