Scholarlink

<p>On the basis of extensive mechanistic research over three decades, Parkinson disease (PD) and related synucleinopathies have been proposed to be combined proteinopathies and lipidopathies. Evidence strongly supports a physiological and pathogenic interplay between the disease-associated protein α-synuclein and lipids, with a demonstrable role for lipids in modulating PD phenotypes in the brain. Here, we refine this hypothesis by proposing PD to be a disease specifically involving metabolic dysregulation of fatty acids, a ‘fatty acidopathy’. We review extensive findings from many laboratories supporting the perspective that PD centres on fatty acid dyshomeostasis — alterations in the fatty acid-ome — as the critical feature of lipid aberration in PD and other α-synucleinopathies. This construct places transient α-synuclein binding to fatty acid side chains of cytoplasmic vesicles as a principal contributor to the biology of PD-relevant α-synuclein–membrane interactions. We propose&#xa0;that α-synuclein–fatty acid interactions in the fatty acid-rich brain are interdependent determinants of the gradual progression from neuronal health to PD, with attendant therapeutic implications.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Parkinson disease is a fatty acidopathy

  • 期刊论文

  • 发表日期：

    2025年10月1日

查看全文
  • Saranna Fanning,
  • Dennis Selkoe

摘要

On the basis of extensive mechanistic research over three decades, Parkinson disease (PD) and related synucleinopathies have been proposed to be combined proteinopathies and lipidopathies. Evidence strongly supports a physiological and pathogenic interplay between the disease-associated protein α-synuclein and lipids, with a demonstrable role for lipids in modulating PD phenotypes in the brain. Here, we refine this hypothesis by proposing PD to be a disease specifically involving metabolic dysregulation of fatty acids, a ‘fatty acidopathy’. We review extensive findings from many laboratories supporting the perspective that PD centres on fatty acid dyshomeostasis — alterations in the fatty acid-ome — as the critical feature of lipid aberration in PD and other α-synucleinopathies. This construct places transient α-synuclein binding to fatty acid side chains of cytoplasmic vesicles as a principal contributor to the biology of PD-relevant α-synuclein–membrane interactions. We propose that α-synuclein–fatty acid interactions in the fatty acid-rich brain are interdependent determinants of the gradual progression from neuronal health to PD, with attendant therapeutic implications.