Reference: Collins BM and Cullen PJ (2025) Separation of powers: A key feature underlying the neuroprotective role of Retromer in age-related neurodegenerative disease? Curr Opin Cell Biol 94:102516

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Abstract


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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Journal Article | Review
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Collins BM, Cullen PJ
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