Retraction Note: VPS35 regulates tau phosphorylation and neuropathology in tauopathy

Vagnozzi, Alana N.; Li, Jianguo; Chiu, Jin; Razmpour, Roshanak; Warfield, Rebecca; Ramirez, Servio H.; Praticò, Domenico

doi:10.1038/s41380-023-01973-9

Cited by 5 publications

(8 citation statements)

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“…8,[22][23][24][25] Conversely, retromer complex dysfunction promotes neurodegeneration by increasing the production of Aβ and reducing pathological tau degradation. 17,[26][27][28] In the present study we showed that human DS neurons manifest an age-dependent retromer complex dysfunction associated with progressive accumulation of Aβ peptides and phosphorylated tau isoforms, and that restoring the complex function, either through overexpression of VPS35 or pharmacological stabilization of the cargo recognition core proteins, results in an amelioration of this AD-like phenotype.…”

Section: Discussionmentioning

confidence: 92%

“…Through its actions within these three pathways, the retromer can influence numerous aspects of neuronal physiology and health including excitability, signaling, survival, lysosomal degradation, and autophagy 8,22–25 . Conversely, retromer complex dysfunction promotes neurodegeneration by increasing the production of Aβ and reducing pathological tau degradation 17,26–28 …”

Section: Discussionmentioning

confidence: 99%

“…Trisomic iPSC‐derived neurons were grown for 23 days post‐differentiation and then incubated with the pharmacological chaperone TPT‐172 (Benjamin Blass, Temple University) diluted in culture media at a total concentration of 25 μM for 48 hours prior to harvest. The TPT‐172 concentration was chosen based on previous studies 26 and an initial screening demonstrating high potency without toxicity for the 25 μM concentration under our experimental conditions.…”

Section: Methodsmentioning

confidence: 99%

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Dysfunction of the retromer complex system contributes to amyloid and tau pathology in a stem cell model of Down syndrome

Curtis

Smith

Blass

et al. 2022

A&D Transl Res & Clin Interv

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Introduction Retromer complex proteins are decreased in Down syndrome (DS) brains and correlate inversely with brain amyloidosis. However, whether retromer dysfunction contributes to the amyloid beta (Aβ) and tau neuropathology of DS remains unknown. Methods Human trisomic induced Pluripotent Stem Cells (iPSCs) and isogenic controls were differentiated into forebrain neurons, and changes in retromer proteins, tau phosphorylated epitopes, and Aβ levels were assessed in euploid and trisomic neurons using western blot and enzyme‐linked immunosorbent assay (ELISA). Genetic overexpression and pharmacological retromer stabilization were used to determine the functional role of the retromer complex system in modulating amyloid and tau pathology. Results Trisomic neurons developed age‐dependent retromer core protein deficiency associated with accumulation of Aβ peptides and phosphorylated tau isoforms. Enhancing retromer function through overexpression or pharmacological retromer stabilization reduced amyloid and tau pathology in trisomic neurons. However, the effect was greater using a pharmacological approach, suggesting that targeting the complex stability may be more effective in addressing this neuropathology in DS. Discussion Our results demonstrate that the retromer complex is directly involved in the development of the neuropathologic phenotype in DS, and that pharmacological stabilization of the complex should be considered as a novel therapeutic tool in people with DS.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Dysfunction of the retromer complex system contributes to amyloid and tau pathology in a stem cell model of Down syndrome

Curtis

Smith

Blass

et al. 2022

A&D Transl Res & Clin Interv

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“…For decades, many studies have focused on the relationship between VPS35 and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases. 10 , 36 Recently, researchers have focused on the role of VPS35 in cancer. 11 , 37 For example, VPS35 is upregulated in breast cancer and promotes cell proliferation by affecting autophagy.…”

Section: Discussionmentioning

confidence: 99%

VPS35 promotes cell proliferation via EGFR recycling and enhances EGFR inhibitors response in gastric cancer

Yu¹,

Feng²,

Sang³

et al. 2023

eBioMedicine

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“…accumulation of pathological tau in a relevant mouse model (Vagnozzi et al, 2019). Moreover, a gene-association study between AD and single nucleotide polymorphisms (SNPs) in 15 retromer-related genes revealed a positive association for several retromer-associated genes (e.g., SNX3, RAB7A, KIAA1033, and SNX1) (Vardarajan et al, 2012).…”

Section: Genetic and Pathological Evidence Linking Retromer And Alzhe...mentioning

confidence: 99%

Beware of Misdelivery: Multifaceted Role of Retromer Transport in Neurodegenerative Diseases

Yoshida

Hasegawa

2022

Front. Aging Neurosci.

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Retromer is a highly integrated multimeric protein complex that mediates retrograde cargo sorting from endosomal compartments. In concert with its accessory proteins, the retromer drives packaged cargoes to tubular and vesicular structures, thereby transferring them to the trans-Golgi network or to the plasma membrane. In addition to the endosomal trafficking, the retromer machinery participates in mitochondrial dynamics and autophagic processes and thus contributes to cellular homeostasis. The retromer components and their associated molecules are expressed in different types of cells including neurons and glial cells, and accumulating evidence from genetic and biochemical studies suggests that retromer dysfunction is profoundly involved in the pathogenesis of neurodegenerative diseases including Alzheimer’s Disease and Parkinson’s disease. Moreover, targeting retromer components could alleviate the neurodegenerative process, suggesting that the retromer complex may serve as a promising therapeutic target. In this review, we will provide the latest insight into the regulatory mechanisms of retromer and discuss how its dysfunction influences the pathological process leading to neurodegeneration.

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Retraction Note: VPS35 regulates tau phosphorylation and neuropathology in tauopathy

Cited by 5 publications

References 0 publications

Dysfunction of the retromer complex system contributes to amyloid and tau pathology in a stem cell model of Down syndrome

Dysfunction of the retromer complex system contributes to amyloid and tau pathology in a stem cell model of Down syndrome

VPS35 promotes cell proliferation via EGFR recycling and enhances EGFR inhibitors response in gastric cancer

Beware of Misdelivery: Multifaceted Role of Retromer Transport in Neurodegenerative Diseases

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