Effect of phenothiazine compounds on the secondary structure and fibrillogenesis of poly-l-lysine
Abstract
Phenothiazine molecules are effective and commonly used antipsychotic drugs, especially in the treatment of schizophrenia. However, they produce strong extrapyramidal side-effects manifested by drug-induced parkinsonism. Because Parkinson's disease as a neurodegenerative illness is associated with the formation of amyloid fibrils in neuronal cells, it is postulated that the development of phenothiazine-induced parkinsonism may be related to the phenothiazine-induced formation of fibrillar aggregates. The effect of phenothiazine compounds (fluphenazine (FPh), chlorpromazine (ChP) and propionylpromazine (PP)) on the fibrillogenesis of poly-l-lysine (PLL) was studied using Fourier-transform infrared (FTIR) spectroscopy supported by principal component analysis (PCA), vibrational circular dichroism (VCD), transmission electron microscopy (TEM) and Congo red binding assay. The fibrillogenesis of PLL is accompanied by fibril formation with charged or uncharged polypeptides with PPII (polyproline-like extended helix), α-helix or β-sheet conformations. All of the phenothiazine molecules investigated effectively reduced the temperature required to induce the formation of β-sheet-rich fibrils from α-helix-rich fibrils of PLL.
Read the paper
Related studies
- Diagnosis and management of glutaric aciduria type I – revised recommendations
- EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas
- Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency
- Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin
- Discovery of Novel Recurrent Mutations in Childhood Early T-Cell Precursor Acute Lymphoblastic Leukemia by Whole Genome Sequencing - a Report From the St Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.