ArticleTranslational psychiatry2022
Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration.
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- ThebioRxiv : the preprint server for biology · 2026Article
- Integrative genomic and functional analyses reveal NINL as a modulator of tau aggregation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Replicable generation and stable maintenance of rhesus macaque iPSCs forFrontiers in cell and developmental biology · 2026Article
- Integrative Genomic and Functional Analyses Reveal NINL as a Modulator of Tau Aggregation.bioRxiv : the preprint server for biology · 2025Article
- A novel lncRNA FAM151B-DT regulates degradation of aggregation prone proteins.Molecular psychiatry · 2025Article
- Cortical versus hippocampal network dysfunction in a human brain assembloid model of epilepsy and intellectual disability.Cell reports · 2025Article
- Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Current Applications of Human Pluripotent Stem Cells in Neuroscience Research and Cell Transplantation Therapy for Neurological Disorders.Stem cell reviews and reports · 2025Review
- Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.Annals of neurology · 2025Article
- GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau.Nature communications · 2025Article
- Somatic and Stem Cell Bank to study the contribution of African ancestry to dementia: African iPSC Initiative.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Transgenic iPSC Lines with Genetically Encoded MitoTimer to Study Mitochondrial Biogenesis in Dopaminergic Neurons with Tauopathy.Biomedicines · 2025Article
- Unraveling the complex role of MAPT-containing H1 and H2 haplotypes in neurodegenerative diseases.Molecular neurodegeneration · 2024Review
- Person-specific differences in ubiquitin-proteasome mediated proteostasis in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Disease-Associated Mutations in Tau Encode for Changes in Aggregate Structure Conformation.ACS chemical neuroscience · 2023Article
- Long non-coding RNA SNHG8 drives stress granule formation in tauopathies.Molecular psychiatry · 2023Article
- Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations.Acta neuropathologica communications · 2023Article
- Conserved gene signatures shared amongFrontiers in molecular biosciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We then used human induced pluripotent stem cell (iPSC)-derived neurons and 3D cerebral organoids from patients carrying the MAPT p.R406W mutation and CRISPR/Cas9, corrected controls to evaluate proteostasis. MAPT p.R406W was sufficient to induce morphological and functional deficits in the lysosomal pathway in iPSC-neurons. These phenotypes were reversed upon correction of the mutant allele with CRISPR/Cas9. Treatment with mTOR inhibitors led to tau degradation specifically in MAPT p.R406W neurons. Together, our findings suggest that MAPT p.R406W is sufficient to cause impaired lysosomal function, which may contribute to disease pathogenesis and serve as a cellular phenotype for drug screening.
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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.