Small Molecule Modulators of α-Synuclein Phase Separation

IF 3.9 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Chemical Neuroscience Pub Date : 2025-08-06 DOI:10.1021/acschemneuro.5c00302

Debabrata Sarkar, Sumangal Roychowdhury, Rajeev Jain, Krishnananda Chattopadhyay* and Biswadip Banerji*,

引用次数: 0

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative condition that affects the brain’s ability to control movement. The disease occurs when nerve cells of the brain become impaired. Alpha-synuclein protein (α-Syn) aggregation followed by fibrillation is a hallmark of PD. Recent studies showed that the liquid–liquid phase separation (LLPS) and droplet formation of α-Syn protein play a crucial role in the pathology of PD. We synthesized novel zwitterionic compounds (3), which inhibited α-Syn phase separation and subsequent formation of fibrillary aggregates in a concentration-dependent manner.

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α-突触核蛋白相分离的小分子调节剂。

帕金森氏症（PD）是一种进行性神经退行性疾病，会影响大脑控制运动的能力。当大脑的神经细胞受损时，这种疾病就会发生。α-突触核蛋白（α-Syn）聚集伴纤颤是帕金森病的标志。近年来的研究表明，α-Syn蛋白的液-液相分离（LLPS）和液滴形成在PD的病理过程中起着至关重要的作用。我们合成了新的两性离子化合物(3)，它们以浓度依赖的方式抑制α-Syn相分离和随后纤维聚集体的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

9.20

自引率

4.00%

发文量

323

审稿时长

1 months

期刊介绍： ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research