{"title":"帕金森病中α-突触核蛋白与膜的相互作用:机制与治疗策略。","authors":"Baoyi Li , Ulf Dettmer","doi":"10.1016/j.nbd.2024.106646","DOIUrl":null,"url":null,"abstract":"<div><div>Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, is marked by the presence of Lewy bodies and Lewy neurites, neuronal lesions containing large amounts of the synaptic protein alpha-synuclein (αS). While the underlying mechanisms of disease progression in PD remain unclear, increasing evidence supports the importance of interactions between αS and cellular membranes in PD pathology. Therefore, understanding the αS-membrane interplay in health and disease is crucial for the development of therapeutic strategies. In this review, we (1) discuss key scenarios of pathological αS-membrane interactions; (2) present in detail therapeutic strategies explicitly reported to modify αS-membrane interactions; and (3) introduce additional therapeutic strategies that may involve aspects of interfering with αS-membrane interaction. This way, we aim to provide a holistic perspective on this important aspect of disease-modifying strategies for PD and other α-synucleinopathies.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"201 ","pages":"Article 106646"},"PeriodicalIF":5.1000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interactions of alpha-synuclein with membranes in Parkinson's disease: Mechanisms and therapeutic strategies\",\"authors\":\"Baoyi Li , Ulf Dettmer\",\"doi\":\"10.1016/j.nbd.2024.106646\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, is marked by the presence of Lewy bodies and Lewy neurites, neuronal lesions containing large amounts of the synaptic protein alpha-synuclein (αS). While the underlying mechanisms of disease progression in PD remain unclear, increasing evidence supports the importance of interactions between αS and cellular membranes in PD pathology. Therefore, understanding the αS-membrane interplay in health and disease is crucial for the development of therapeutic strategies. In this review, we (1) discuss key scenarios of pathological αS-membrane interactions; (2) present in detail therapeutic strategies explicitly reported to modify αS-membrane interactions; and (3) introduce additional therapeutic strategies that may involve aspects of interfering with αS-membrane interaction. This way, we aim to provide a holistic perspective on this important aspect of disease-modifying strategies for PD and other α-synucleinopathies.</div></div>\",\"PeriodicalId\":19097,\"journal\":{\"name\":\"Neurobiology of Disease\",\"volume\":\"201 \",\"pages\":\"Article 106646\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969996124002468\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969996124002468","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Interactions of alpha-synuclein with membranes in Parkinson's disease: Mechanisms and therapeutic strategies
Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, is marked by the presence of Lewy bodies and Lewy neurites, neuronal lesions containing large amounts of the synaptic protein alpha-synuclein (αS). While the underlying mechanisms of disease progression in PD remain unclear, increasing evidence supports the importance of interactions between αS and cellular membranes in PD pathology. Therefore, understanding the αS-membrane interplay in health and disease is crucial for the development of therapeutic strategies. In this review, we (1) discuss key scenarios of pathological αS-membrane interactions; (2) present in detail therapeutic strategies explicitly reported to modify αS-membrane interactions; and (3) introduce additional therapeutic strategies that may involve aspects of interfering with αS-membrane interaction. This way, we aim to provide a holistic perspective on this important aspect of disease-modifying strategies for PD and other α-synucleinopathies.
期刊介绍:
Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.