ArticleActa neuropathologica2016
Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation.
Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 89 citations in OpenAlex.
- Proximity labeling reveals unique and shared interactomes of unmodified and pyroglutamate amyloid beta in human hippocampus in Alzheimer's disease.Research square · 2026Article
- Comparative evaluation of reference-free transcriptomic deconvolution highlights the importance of biological validation in astrocytes across Alzheimer's disease.Frontiers in bioinformatics · 2026Article
- CHIP protects lysosomes from CLN4 mutant-induced membrane damage.Nature cell biology · 2025Article
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Uncovering the role of the Hsp40 family member cysteine string protein-α in mouse platelets.Blood advances · 2025Article
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Neuronal lipofuscinosis caused by Kufs disease/CLN4 DNAJC5 mutations but not by a CSPα/DNAJC5 deficiency.Science advances · 2025Article
- Review
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Cell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone.Science advances · 2024Article
- Decoding transcriptomic signatures of cysteine string protein alpha-mediated synapse maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- L116 Deletion in CSPα Promotes α-Synuclein Aggregation and Neurodegeneration.Molecular neurobiology · 2024Article
- A Caenorhabditis elegans model of autosomal dominant adult-onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic.Human molecular genetics · 2023Article
- Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation.Autophagy · 2023Article
- Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson's Disease.International journal of molecular sciences · 2022Article
- Current knowledge of protein palmitoylation in gliomas.Molecular biology reports · 2022Review
- Mass spectrometry-based proteomics in neurodegenerative lysosomal storage disorders.Molecular omics · 2022Review
- Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function.PLoS biology · 2022Article
- Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential.International journal of molecular sciences · 2022Review
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Authors and funding
14 authors at 8 institutions in 2 countries.
Funding
Abstract
Neuronal ceroid lipofuscinoses (NCL) are a group of inherited neurodegenerative disorders with lysosomal pathology (CLN1-14). Recently, mutations in the DNAJC5/CLN4 gene, which encodes the presynaptic co-chaperone CSPα were shown to cause autosomal-dominant NCL. Although 14 NCL genes have been identified, it is unknown if they act in common disease pathways. Here we show that two disease-associated proteins, CSPα and the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1/CLN1) are biochemically linked. We find that in DNAJC5/CLN4 patient brains, PPT1 is massively increased and mis-localized. Surprisingly, the specific enzymatic activity of PPT1 is dramatically reduced. Notably, we demonstrate that CSPα is depalmitoylated by PPT1 and hence its substrate. To determine the consequences of PPT1 accumulation, we compared the palmitomes from control and DNAJC5/CLN4 patient brains by quantitative proteomics. We discovered global changes in protein palmitoylation, mainly involving lysosomal and synaptic proteins. Our findings establish a functional link between two forms of NCL and serve as a springboard for investigations of NCL disease pathways.
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