Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Nov. 9, 2023

Abstract Peptides and their mimetics are increasingly recognised as drug-like molecules, particularly for intracellular protein-protein interactions too large inhibition by small inaccessible to larger biologics. In the past two decades, evidence associating misfolding aggregation of alpha-synuclein strongly implicates this protein in disease onset progression Parkinson’s related synucleinopathies. The subsequent formation toxic, intracellular, Lewy body deposits, which is a major component, key diagnostic hallmark disease. To reach therapeutic site action, peptides must both cross blood-brain barrier enter dopaminergic neurons prevent these inclusions. review, we describe summarise current efforts made development directly engage with intention modulating aggregation, importantly, toxicity. This rapidly expanding field great socioeconomic impact; molecules harbour significant promise therapeutics, or early biomarkers during prodromal stages, both. As age-dependent conditions, an increasing global life expectancy means prevalence rising. No treatments exist either slow progression. It therefore crucial that drugs developed conditions before health care social capacities become overrun.

Language: Английский

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Trends in parkinson’s disease mortality in China from 2004 to 2021: a joinpoint analysis

BMC Public Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 19, 2024

This study aimed to analyze the trends of Parkinson's disease (PD) mortality rates among Chinese residents from 2004 2021, provide evidence for formulation PD prevention and control strategies improve quality life residents.

Language: Английский

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An N-terminal alpha-synuclein fragment binds lipid vesicles to modulate lipid-induced aggregation

Cell Reports Physical Science, Journal Year: 2023, Volume and Issue: 4(9), P. 101563 - 101563

Published: Aug. 24, 2023

Misfolding and aggregation of alpha-synuclein (αS) into toxic conformations is involved in numerous neurodegenerative diseases. In Parkinson's disease (PD), this occurs within dopaminergic neurons, causing cell death symptoms. During αS aggregation, many protein-protein interactions (PPIs) form over broad flat protein surfaces, limiting potential for small-molecule intervention. Peptides, however, harbor great therapeutic promise since they can selectively engage with modulate the large surface areas yet are small enough to function as druggable agents if suitably structured. Here, we explore first 25 residues (αS1–25) a template peptide-based antagonists. We report that αS1–25 inhibits lipid-induced dose-dependent manner. functions by binding lipids prevent binding, both peptide requiring lipid inhibition occur. These findings present mechanistic route treatment or prevention PD.

Language: Английский

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Identification of α-Synuclein Aggregation Inhibitors via High-Throughput Screening

Neuromethods, Journal Year: 2024, Volume and Issue: unknown, P. 61 - 85

Published: Dec. 26, 2024

Language: Английский

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