anti-Ceroid-Lipofuscinosis, Neuronal 3 (CLN3) Antibodies

Human Ceroid-Lipofuscinosis, Neuronal 3 (CLN3) interaction partners

1. Overexpression of CLN3 contributes to tumor progression and and metastasis in hepatocellular carcinoma.

2. We describe a patient who initially presented with CLN3-associated isolated retinal degeneration but developed adult-onset neurologic decline, contrasting with the previous exclusive association of the R405W mutation with isolated vision loss.

3. Our case study shows that (1) non-syndromic CLN3 disease leads to rod and delayed primary cone degeneration resulting in constricting peripheral field and enlarging central scotoma and, (2) the c.175G>A CLN3 mutation, altered splicing of the CLN3 gene.

4. the results of this study indicate that Cln3 functions in both conventional and unconventional protein secretion and that loss of Cln3 results in deregulated secretion during early development. Importantly, this is the first evidence in any system linking CLN3 function to protein secretion.

5. AAV2-CLN3 was efficacious in restoring full-length CLN3 transcript and protein in patient-specific fibroblasts and iPSC-derived retinal neurons. When injected into the subretinal space of wild-type mice, purified AAV2-CLN3 did not show any evidence of retinal toxicity

6. The lysosomal enzyme cathepsin D (CTSD) mediates the proteolytic cleavage of PSAP precursor into saposins A-D. Myc-CLN3 colocalized with CTSD and activity of CTSD decreased as myc-CLN3 expression increased, and clearly decreased under hyperosmotic conditions

7. This is the first detailed morphological evaluation of CLN3 patients in the first years after the subjective onset of ocular symptoms. CLN3 is characterized by an early degeneration predominant of the first and second neuron compared to other macular and generalized retinal dystrophies.

8. The age at onset and natural progression of retinal disease differs greatly between syndromic and nonsyndromic CLN3 disease, which may be associated with genotypic differences.

9. CLN3 knockdown inhibits cell proliferation and induces G0/G1 cell cycle arrest in the A2780 cell line and its drug-resistant sub-lines.

10. The membrane topology of human CLN3 protein.

11. The eyes and vision of heterozygous carriers of CLN3 disease showed normal features when compared to a control group, which controverts a previously suggested retinal dysfunction in these subjects.

12. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3- cells

13. These results further support an important role for the CLN3 protein in intracellular Ca(2+) handling and in autophagic pathway flux and establish a powerful new platform for therapeutic screening.

14. CLN3 mutation is associated with neuronal ceroid lipofuscinosis.

15. Genetic testing for CLN3 should be considered in autophagic vacuolar myopathy (AVM), with autophagic vacuoles and sarcolemmal features.

16. CLN3 was identified as a novel disease gene for non-syndromic retinal diseases as supported by five unrelated patient families in this study.

17. CLN3 is involved in the response and adaptation to cellular stress.

18. Protein interaction mapping analysis suggests CLN3 is involved in transmembrane transport, lipid homeostasis, neuronal excitability and link it to G-protein signaling and protein folding/sorting in the endoplasmic reticulum.

19. The data presented in this study provide novel insights into the role of CLN3 in late endosomal/lysosomal membrane transport.

20. Btn1 controls retrograde sorting by regulating SNARE phosphorylation and assembly, a process that may be adversely affected in Batten Disease patients.

Mouse (Murine) Ceroid-Lipofuscinosis, Neuronal 3 (CLN3) interaction partners

1. These results show that CLN3 deficiency alters antigen presenting cells, which can be a major contributor to the autoimmune response in juvenile neuronal ceroid lipofuscinosis.

2. Loss of CLN3 protein leads to early presynaptic changes and altered short-term plasticity in a mouse model of juvenile Batten disease.

3. Our subcellular localization study in neurons refines the localization and subcellular targeting of CLN3 to late endosomal-lysosomal compartments

4. findings in two distinct lysosome-related degradative pathways constitute the first description of a deficit in the retinal pigment epithelium caused by loss of CLN3

5. The small GTPase Cdc42 is misregulated in the absence of CLN3, and thus may be a common link to multiple cellular defects.

6. Rssults suggested that CLN2, CLN3 and CLN5 genes may play an important role in early embryonal neurogenesis.

7. The aim of our study was to investigate the visual disease progression in the Cln3 (Deltaex7/8) mice.

8. CLN3 facilitates transport of microdomain-associated proteins.

9. results demonstrate altered glutamate receptor function in Cln3(Deltaex7/8) neurons and suggest that both AMPA and NMDA receptors are potential therapeutic targets in juvenile neuronal ceroid lipofuscinosis

10. The migration defect in Cln3(-/-) results, in part, from the loss of the CLN3-myosin-IIB interaction.

11. Findings suggest an osmoregulated role for CLN3p in renal medullary control of water and K(+) balance.

12. Cln3(Deltaex7/8) knock-in mice with the common juvenile-onset neuronal ceroid lipofuscinosis (JNCL; Batten disease) mutation exhibit progressive neurologic disease that begins before birth.

13. we investigated endogenous Cln3p expression using two peptide antibodies raised against two distinct epitopes of murine Cln3p.

14. CLN3 defect may result in altered mitochondrial function in eye but not other tissue.

15. The Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was at 14 months of age.

16. AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein CLN3 via its dileucine motif

17. Cnl3 mutant mice revealed a pronounced loss of neurons within individual laminae of somatosensory cortex of affected mice and the novel finding of a loss of sensory relay thalamic neurons.

18. cln3 has a role in pathology of Batten disease, as shown by NMR metabolomic analysis of the mouse model

19. Having previously demonstrated that Cln3(-/-) mice have decreased optic nerve axonal density, we now demonstrate a decrease in nerve conduction.

20. Vulnerability of CLN3 knock-out or CLN3 deletion (1-153)-expressing neuronal cells to Ca(2+)-induced cell death may be mediated by calsenilin.

Cow (Bovine) Ceroid-Lipofuscinosis, Neuronal 3 (CLN3) interaction partners

1. The candidate genes for bovine Neuronal Ceroid Lipofuscinosis, CLN3, CLN5 and CLN6, have been mapped to facilitate linkage analysis in cattle and sheep.