ArticleScientific reports2017
Primary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- CHIP protects lysosomes from CLN4 mutant-induced membrane damage.Nature cell biology · 2025Article
- Neuronal lipofuscinosis caused by Kufs disease/CLN4 DNAJC5 mutations but not by a CSPα/DNAJC5 deficiency.Science advances · 2025Article
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- Tissue distribution of cysteine string protein/DNAJC5 in C. elegans analysed by CRISPR/Cas9-mediated tagging of endogenous DNJ-14.Cell and tissue research · 2024Article
- Proximity labelling reveals effects of disease-causing mutation on the DNAJC5/cysteine string protein α interactome.The Biochemical journal · 2024Article
- Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation.Autophagy · 2023Article
- Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration.Translational psychiatry · 2022Article
- CSPα in neurodegenerative diseases.Frontiers in aging neuroscience · 2022Review
- Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).Frontiers in cell and developmental biology · 2022Review
- Safeguarding Lysosomal Homeostasis by DNAJC5/CSPα-Mediated Unconventional Protein Secretion and Endosomal Microautophagy.Frontiers in cell and developmental biology · 2022Review
- Article
- Autosomal dominant neuronal ceroid lipofuscinosis: Clinical features and molecular basis.Clinical genetics · 2021Review
- Fly model sheds light on brain disease.eLife · 2019Article
- Differences in the prognosis of gastric cancer patients of different sexes and races and the molecular mechanisms involved.International journal of oncology · 2019Article
- AeLife · 2019Article
- Immature O-glycans recognized by the macrophage glycoreceptor CLEC10A (MGL) are induced by 4-hydroxy-tamoxifen, oxidative stress and DNA-damage in breast cancer cells.Cell communication and signaling : CCS · 2019Article
- TheScience translational medicine · 2019Article
- TREM2 brain transcript-specific studies in AD and TREM2 mutation carriers.Molecular neurodegeneration · 2019Article
- Depalmitoylation by Palmitoyl-Protein Thioesterase 1 in Neuronal Health and Degeneration.Frontiers in synaptic neuroscience · 2019Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the co- chaperone protein, CSPα, cause an autosomal dominant, adult-neuronal ceroid lipofuscinosis (AD-ANCL). The current understanding of CSPα function exclusively at the synapse fails to explain the autophagy-lysosome pathway (ALP) dysfunction in cells from AD-ANCL patients. Here, we demonstrate unexpectedly that primary dermal fibroblasts from pre-symptomatic mutation carriers recapitulate in vitro features found in the brains of AD-ANCL patients including auto-fluorescent storage material (AFSM) accumulation, CSPα aggregates, increased levels of lysosomal proteins and lysosome enzyme activities. AFSM accumulation correlates with CSPα aggregation and both are susceptible to pharmacological modulation of ALP function. In addition, we demonstrate that endogenous CSPα is present in the lysosome-enriched fractions and co-localizes with lysosome markers in soma, neurites and synaptic boutons. Overexpression of CSPα wild-type (WT) decreases lysotracker signal, secreted lysosomal enzymes and SNAP23-mediated lysosome exocytosis. CSPα WT, mutant and aggregated CSPα are degraded mainly by the ALP but this disease-causing mutation exhibits a faster rate of degradation. Co-expression of both WT and mutant CSPα cause a block in the fusion of autophagosomes/lysosomes. Our data suggest that aggregation-dependent perturbation of ALP function is a relevant pathogenic mechanism for AD-ANCL and supports the use of AFSM or CSPα aggregation as biomarkers for drug screening purposes.
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