Abstract

This is a project to determine the molecular basis of the late infantile form of neuronal ceroid lipofuscinosis (LINCL). The starting point is the successful cloning of the cDNA and determination of mutations in the CLN2 protein.
The specific aims are to (1) determine the structure of the gene; (2) Identify mutations in the CLN2 gene; (3) develop a mouse model of the disease; and (4) characterize the CLN2 protein and its function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS037918-02
Application #
2892457
Study Section
Medical Biochemistry Study Section (MEDB)
Program Officer
Spinella, Giovanna M
Project Start
1998-04-01
Project End
2003-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Medicine & Dentistry of NJ
Department
Pharmacology
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854

  Publications

Solé-Domènech, Santiago; Rojas, Ana V; Maisuradze, Gia G et al. (2018) Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar A? by multiple endoproteolytic cleavages within the ?-sheet domain. Proc Natl Acad Sci U S A 115:1493-1498
Nemtsova, Yuliya; Wiseman, Jennifer A; El-Banna, Mukarram et al. (2018) Inducible transgenic expression of tripeptidyl peptidase 1 in a mouse model of late-infantile neuronal ceroid lipofuscinosis. PLoS One 13:e0192286
Sleat, David E; Tannous, Abla; Sohar, Istvan et al. (2017) Proteomic Analysis of Brain and Cerebrospinal Fluid from the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Potential Biomarkers. J Proteome Res 16:3787-3804
Jadot, Michel; Boonen, Marielle; Thirion, Jaqueline et al. (2017) Accounting for Protein Subcellular Localization: A Compartmental Map of the Rat Liver Proteome. Mol Cell Proteomics 16:194-212
Wiseman, Jennifer A; Meng, Yu; Nemtsova, Yuliya et al. (2017) Chronic Enzyme Replacement to the Brain of a Late Infantile Neuronal Ceroid Lipofuscinosis Mouse Has Differential Effects on Phenotypes of Disease. Mol Ther Methods Clin Dev 4:204-212
Meng, Yu; Wiseman, Jennifer A; Nemtsova, Yuliya et al. (2017) A Basic ApoE-Based Peptide Mediator to Deliver Proteins across the Blood-Brain Barrier: Long-Term Efficacy, Toxicity, and Mechanism. Mol Ther 25:1531-1543
Sleat, David E; Gedvilaite, Erika; Zhang, Yeting et al. (2016) Analysis of large-scale whole exome sequencing data to determine the prevalence of genetically-distinct forms of neuronal ceroid lipofuscinosis. Gene 593:284-91
Huang, Ling; Pike, Douglas; Sleat, David E et al. (2014) Potential pitfalls and solutions for use of fluorescent fusion proteins to study the lysosome. PLoS One 9:e88893
Meng, Yu; Sohar, Istvan; Sleat, David E et al. (2014) Effective intravenous therapy for neurodegenerative disease with a therapeutic enzyme and a peptide that mediates delivery to the brain. Mol Ther 22:547-553
Meng, Yu; Sohar, Istvan; Wang, Lingling et al. (2012) Systemic administration of tripeptidyl peptidase I in a mouse model of late infantile neuronal ceroid lipofuscinosis: effect of glycan modification. PLoS One 7:e40509

Showing the most recent 10 out of 35 publications