Snake Venom-Inspired Novel Peptides Protect Caenorhabditis elegans against Paraquat-Induced Parkinson's Pathology

• Tipo: Artigo em Revista Científica Internacional
• Data: 2025

Autores

Madhubala, D (Autor) Outra; Mahato, R (Autor) Outra; Saikia, K (Autor) Outra; Patra, A (Autor) Outra; Pedro A Fernandes (Autor) FCUP; Kumar, A (Autor) Outra; Khan, MR (Autor) Outra; Mukherjee, AK (Autor) Outra

Revista

Título: Acs Chemical Neuroscience

ISSN: 1948-7193

Editora: American Chemical Society

Indexação

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Outras Informações

ID Authenticus: P-018-BRZ

DOI: 10.1021/acschemneuro.4c00576

Abstract (EN): The in vivo protective mechanisms of two low-molecular-mass (similar to 1.4 kDa) novel custom peptides (CPs) against paraquat-induced neurodegenerative dysfunction in the Caenorhabditis elegans model were deciphered. CPs prevented the paraquat from binding to the nerve ring adjacent to the pharynx in C. elegans (wild-type) by stable and high-affinity binding to the tyrosine-protein kinase receptor CAM-1, resulting in significant inhibition of paraquat-induced toxicity by reducing the production of reactive oxygen species, mitochondrial membrane depolarization, and chemosensory dysfunction. The CPs inhibited paraquat-induced dopaminergic neuron degeneration and alpha-synuclein protein expression, the hallmarks of Parkinson's disease, in transgenic BZ555 and NL5901 strains of C. elegans. Transcriptomic, functional proteomics, and quantitative reverse transcription-polymerase chain reaction analyses show that CPs prevented the increased expression of the genes involved in the skn-1 downstream pathway, thereby restoring paraquat-mediated oxidative stress, apoptosis, and neuronal damage in C. elegans. The ability of CPs to repair paraquat-induced damage was demonstrated by a network of gene expression profiles, illustrating the molecular relationships between the regulatory proteins.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 22