Shashi Prakash Patel, Tejas Nikam, Bhargavi Sreepathi, Vijayshree S. Karankar, Ankita Jaiswal, Salumuri Vamsi Vardhan, Anika Rana, Vanshu Toga, Nidhi Srivastava, Shubhini A Saraf and Saurabh Awasthi*,
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Here, we review recent studies examining the effects of various crowding agents, such as polysaccharides, polyethylene glycol, and proteins like BSA and lysozyme on the behaviors of aggregation of several amyloidogenic peptides and proteins, including amylin, huntingtin, tau, α-synuclein, prion, and amyloid-β. We also summarize how the aggregation kinetics, thermodynamic stability, and morphology of amyloid fibrils are altered significantly in the presence of crowding agents. In addition, we also discuss the molecular basis underlying the modulation of amyloidogenic aggregation, focusing on changes in the protein conformation, and the nucleation mechanism. The molecular understanding of the effects of macromolecular crowding on amyloid aggregation is essential for revealing disease pathologies and identifying possible therapeutic targets. Thus, this review offers a perspective on the complex interplay between protein aggregation and the crowded cellular environment <i>in vivo</i> and explains the relevance of crowding in the context of neurodegenerative disorders.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unraveling the Molecular Jam: How Crowding Shapes Protein Aggregation in Neurodegenerative Disorders\",\"authors\":\"Shashi Prakash Patel, Tejas Nikam, Bhargavi Sreepathi, Vijayshree S. 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Unraveling the Molecular Jam: How Crowding Shapes Protein Aggregation in Neurodegenerative Disorders
Protein misfolding and aggregation are the hallmarks of neurodegenerative diseases including Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, and prion diseases. A crowded cellular environment plays a crucial role in modulating protein aggregation processes in vivo and the pathological aggregation of proteins linked to different neurodegenerative disorders. Here, we review recent studies examining the effects of various crowding agents, such as polysaccharides, polyethylene glycol, and proteins like BSA and lysozyme on the behaviors of aggregation of several amyloidogenic peptides and proteins, including amylin, huntingtin, tau, α-synuclein, prion, and amyloid-β. We also summarize how the aggregation kinetics, thermodynamic stability, and morphology of amyloid fibrils are altered significantly in the presence of crowding agents. In addition, we also discuss the molecular basis underlying the modulation of amyloidogenic aggregation, focusing on changes in the protein conformation, and the nucleation mechanism. The molecular understanding of the effects of macromolecular crowding on amyloid aggregation is essential for revealing disease pathologies and identifying possible therapeutic targets. Thus, this review offers a perspective on the complex interplay between protein aggregation and the crowded cellular environment in vivo and explains the relevance of crowding in the context of neurodegenerative disorders.
期刊介绍:
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.