RETRACTED ARTICLE: VPS35 regulates tau phosphorylation and neuropathology in tauopathy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/s41380-019-0453-x

Cited by 44 publications

(70 citation statements)

References 44 publications

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“…Furthermore, VPS35 de ciency enhanced AD neuropathology in a Tg2576 mouse model of AD [23]. A current report identi ed that VPS35 regulates tau phosphorylation and neuropathology in tauopathies, such as progressive supranuclear palsy (PSP) and Pick's disease [70].…”

Section: Discussionmentioning

confidence: 89%

Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N

Bono¹,

Miyauchi-Hara²,

Sumi³

et al. 2020

Preprint

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Mutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons from PD patients with the VPS35 D620N mutation and addressed relevant disease mechanisms. In the disease group, dopaminergic (DA) neurons underwent extensive apoptotic cell death. The movement of Rab5a- or Rab7a-positive endosomes was slower, and the endosome fission and fusion frequencies were lower in the PD group than in the healthy control group. Interestingly, vesicles positive for cation-independent mannose 6-phosphate receptor transported by retromers were abnormally localized in glial cells derived from patient iPSCs. Furthermore, we found a-synuclein accumulation in TH positive DA neurons. Our results demonstrate the induction of cell death, endosomal dysfunction and a-synuclein accumulation in neural cells of the PD group. PARK17 patient-derived iPSCs provide an excellent experimental tool for understanding the pathophysiology underlying PD.

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Section: Discussionmentioning

confidence: 89%

Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N

Bono¹,

Miyauchi-Hara²,

Sumi³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…A key caveat to our understanding of how VPS35 mutations link to Parkinson's is that, to date, no VPS35 mutation brains have come to post-mortem pathological analysis, and therefore it is not known if VPS35 PD is a synucleinopathy. It is of interest to note that VPS35 (D620N) mutation causes tau pathology in mice (Chen et al, 2019) and its levels are reduced in two primary tauopathies progressive supranuclear palsy and Pick's disease (Vagnozzi et al, 2019).…”

Section: Valosin Containing Proteins (Vps35 and Vps13c)mentioning

confidence: 99%

Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies

Ebanks

Lewis

2020

Front. Neurosci.

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Parkinson's disease (PD) is a common age-related neurodegenerative disorder with disabling motor symptoms and no available disease modifying treatment. The majority of the PD cases are of unknown etiology, with both genetics and environment playing important roles. Over the past 25 years, however, genetic analysis of patients with familial history of Parkinson's and, latterly, genome wide association studies (GWAS) have provided significant advances in our understanding of the causes of the disease. These genetic insights have uncovered pathways that are affected in both genetic and sporadic forms of PD. These pathways involve oxidative stress, abnormal protein homeostasis, mitochondrial dysfunction, and lysosomal defects. In addition, newly identified PD genes and GWAS nominated genes point toward synaptic changes involving vesicles. This review will highlight the genes that contribute PD risk relating to intracellular vesicle trafficking and their functional consequences. There is still much to investigate on this newly identified and converging pathway of vesicular dynamics and PD, which will aid in better understanding and suggest novel therapeutic strategies for PD patients.

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“…Furthermore, VPS35 de ciency enhanced AD neuropathology in a Tg2576 mouse model of AD [22]. A current report identi ed that VPS35 regulates tau phosphorylation and neuropathology in tauopathies, such as progressive supranuclear palsy (PSP) and Pick's disease [60].…”

Section: Discussionmentioning

confidence: 89%

Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N

Bono¹,

Miyauchi-Hara²,

Sumi³

et al. 2020

Preprint

View full text Add to dashboard Cite

Mutations in the Vacuolar protein sorting 35 ( VPS35 ) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons from PD patients with theVPS35D620N mutation and addressed relevant disease mechanisms. In the disease group, dopaminergic (DA) neurons underwent extensive apoptotic cell death. Furthermore, the movement of Rab5a - or Rab7a - positive endosomes was slower , and the endosome fission and fusion frequencies were lower in the PD group than in the healthy control group . Interestingly , vesicles positive for cation-independent mannose 6-phosphate receptor transported by retromers were abnormally localized in glia-like cells derived from patient iPSCs. These results suggest that VPS35 mutation causes endosomal dysfunction in neural cells in PARK17.

show abstract

RETRACTED ARTICLE: VPS35 regulates tau phosphorylation and neuropathology in tauopathy

Cited by 44 publications

References 44 publications

Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N

Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N

Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies

Endosomal Dysfunction in iPSC-Derived Neural Cells from Parkinson’s Disease Patients with VPS35 D620N

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