ReviewMolecular neurodegeneration2026
Retromer-targeted therapy for neurodegenerative diseases.
Review in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases characterized by dysfunction of the endosomal-lysosomal system (ELS). Four shared neurodegenerative mechanisms across ALS, PD and AD are regulated by the ELS, namely proteostasis and related protein misfolding, mitochondrial function, neurotransmission and neuroinflammation. These mechanisms are interconnected, contributing to neurodegeneration in a "snowball" manner. The retromer, a multimeric, evolutionarily conserved protein complex involved in intracellular protein trafficking, is at the crossroad of these neurodegenerative processes. This narrative review focuses on exploring the retromer structure, function as a master regulator of the ELS, and how this impacts proteostasis, mitochondrial biogenesis and homeostasis, neurotransmission and neuroinflammation across neurodegenerative diseases. We explore how alterations in retromer function can play an important role in neurodegeneration and discuss the impact of genetic and pharmacological manipulations of VPS35, one of the main retromer subunits. In vitro and in vivo studies have identified that the retromer enhances the activity of protein degradation pathways via the ELS, namely macroautophagy, chaperone-mediated autophagy, and the ELS itself, with concomitant reduction in misfolded protein levels. Also, in some model systems, when the retromer role is enhanced or restored, mitochondrial function is rescued, dysfunctional neurotransmission is restored, and the damaging effects of neuroinflammation are dampened. Lastly, we highlight the role of a novel pharmacological class of agents that enhance retromer function as a strategy for potentially slowing the progression of these neurodegenerative diseases in in vivo models of PD and ALS. We discuss the challenges in targeting the retromer, current limitations and potential off-target effects of retromer enhancement. Overall, the retromer regulates shared mechanisms across neurodegenerative diseases and retromer enhancers could represent a novel disease-modifying strategy in AD, PD and ALS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.