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SCIENTIFIC LITERATURE · MED

Separation of powers: A key feature underlying the neuroprotective role of Retromer in age-related neurodegenerative disease?

Curr Opin Cell Biol · 2025-04-19

DOI: 10.1016/j.ceb.2025.102516PMID: 40253888

Open accessresearch-article; Review; Journal ArticleOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

The retromer complex was discovered in Saccharomyces cerevisiae as a multiprotein, pentameric assembly essential for recycling of integral membrane cargo proteins through the endosomal network [1,2]. We now understand how retromer is assembled, its membrane architecture, and how it selects proteins for recycling [3-6]. Conserved across eukaryotes, analyses have revealed retromer's role in organism development, and homeostasis and has linked retromer defects with age-related Alzheimer's disease and Parkinson's disease and other neurological disorders [3,5,7]. Indeed, stabilizing retromer function is now actively considered a therapeutic strategy [8]. Here, we reflect on its structural and functional evolution rather than overviewing retromer biology (see, e.g. [5,7]). Specifically, we clarify the organization of the human retromer to provide greater focus for future research, especially within the context of retromer's function in neuroprotection.

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