ArticleHuman molecular genetics2017
Impaired axonal retrograde trafficking of the retromer complex augments lysosomal deficits in Alzheimer's disease neurons.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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
40 citing papers in PubMed, 53 citations in OpenAlex.
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Mitochondrial Damage and Autophagy Dysregulation in Alzheimer's Disease: Mechanisms and Therapeutic Opportunities.Neurochemical research · 2025Review
- Autophagy in alzheimer disease pathogenesis and its therapeutic values.Autophagy reports · 2025Review
- Adult-onset deactivation of autophagy leads to loss of synapse homeostasis and cognitive impairment, with implications for alzheimer disease.Autophagy · 2024Article
- Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues.International journal of molecular sciences · 2024Review
- ARF4-mediated retrograde trafficking as a driver of chemoresistance in glioblastoma.Neuro-oncology · 2024Article
- VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.Expert opinion on therapeutic targets · 2024Review
- A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation.Autophagy · 2024Article
- Endolysosomal impairment by binding of amyloid beta or MAPT/Tau to V-ATPase and rescue via the HYAL-CD44 axis in Alzheimer disease.Autophagy · 2023Article
- The Highs and Lows of Memantine-An Autophagy and Mitophagy Inducing Agent That Protects Mitochondria.Cells · 2023Article
- Article
- Diversity of retromer-mediated vesicular trafficking pathways in plants.Frontiers in plant science · 2023Review
- Endosomal trafficking and related genetic underpinnings as a hub in Alzheimer's disease.Journal of cellular physiology · 2022Review
- Are mitophagy enhancers therapeutic targets for Alzheimer's disease?Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Long-term running exercise alleviates cognitive dysfunction in APP/PSEN1 transgenic mice via enhancing brain lysosomal function.Acta pharmacologica Sinica · 2022Article
- Neuronal endolysosomal transport and lysosomal functionality in maintaining axonostasis.The Journal of cell biology · 2022Review
- Regulation of neuronal autophagy and the implications in neurodegenerative diseases.Neurobiology of disease · 2022Review
- Beware of Misdelivery: Multifaceted Role of Retromer Transport in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Decreased anterograde transport coupled with sustained retrograde transport contributes to reduced axonal mitochondrial density in tauopathy neurons.Frontiers in molecular neuroscience · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lysosomal proteolysis is essential for the quality control of intracellular components and the maintenance of cellular homeostasis. Lysosomal alterations have been implicated as one of the main cellular defects contributing to the onset and progression of Alzheimer's disease (AD). However, the mechanism underlying lysosomal deficits in AD remains poorly understood. Here, we reveal that lysosomal deficits are attributed to retromer dysfunction induced by altered retromer trafficking in the axon of AD-related mutant human amyloid precursor protein (hAPP) transgenic (Tg) mouse neurons. We demonstrate that retrograde transport of retromer is impaired, leading to its significant reduction in the soma and abnormal retention within late endosomes in distal axons of mutant hAPP neurons. Therefore, retromer-mediated endosome-to-Golgi retrieval of cation-independent mannose-6-phosphate receptors (CI-MPR) in the soma is disrupted in mutant hAPP neurons, causing defects in lysosome biogenesis. Such defects result in protease deficiency in lysosomes and impaired lysosomal proteolysis, as evidenced by aberrant accumulation of sequestered substrates within lysosomes. Intriguingly, enhancement of retrograde transport in mutant hAPP neurons facilitates the trafficking of axonal retromer toward the soma and thus enhances protease transport to lysosomes, thereby restoring lysosomal proteolytic activity. Taken together, our study provides new insights into the regulation of retromer trafficking through retrograde axonal transport to fulfil its function in promoting lysosome biogenesis in the soma, suggesting a potential approach for rescuing lysosomal proteolysis deficits in AD.
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.