Projects / Programmes
Cathepsin F, a novel cysteine protease involved in neuronal ceroid lipofuscinosis
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
neurodegeneration, neuronal ceroid lipofuscinosis, programmed cell death, cysteine cathepsins
Researchers (6)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
18801 |
PhD Marko Fonović |
Biochemistry and molecular biology |
Researcher |
2007 - 2010 |
187 |
| 2. |
26451 |
Martina Klarić |
Biochemistry and molecular biology |
Junior researcher |
2007 - 2009 |
12 |
| 3. |
14829 |
PhD Veronika Stoka |
Biochemistry and molecular biology |
Head |
2007 - 2010 |
237 |
| 4. |
15969 |
Ivica Štefe |
Biochemistry and molecular biology |
Technical associate |
2007 - 2010 |
36 |
| 5. |
07561 |
PhD Boris Turk |
Biochemistry and molecular biology |
Researcher |
2007 - 2009 |
1,037 |
| 6. |
01085 |
PhD Vito Turk |
Biochemistry and molecular biology |
Researcher |
2007 - 2010 |
1,490 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0106 |
Jožef Stefan Institute |
Ljubljana |
5051606000 |
90,812 |
Abstract
The neuronal ceroid lipofuscinoses are a group of ten autosomal recessively inherited storage disorders characterized by lysosomal inclusions of autofluorescent lipofuscins, rapid neurodegenerative progression and premature death. Recently the deficiency of a lysosomal cysteine protease cathepsin F was found to result in a lysosomal storage defect and progressive neurological features in cathepsin F deficient mice. Therefore, the aim of this project is to shed light on the mechanisms of activation of neuronal cell death focusing on signal transduction pathways involving the lysosomal, mitochondrial and endoplasmic reticulum systems, respectively. The work will be carried out on neuronal (SH-SY5Y) and glial (T98g) cellular models. A deeper understanding of the structure-function relationship of cathepsin F may also reveal the role of this enzyme in adult neuronal ceroid lipofuscinosis (Kufs' disease) and its potential as a novel prognostic/diagnostic marker. In addition, this project may also contribute to the understanding of other neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases where accumulation of storage proteins and activation of apoptotic and/or autophagic cell death pathways was observed.
Significance for science
The research on cysteine cathepsins regained importance due to their role in several diseases such as neurodegeneration, cancer, ostheoporosis, autoimmune diseases as well as genetic disorders. This project tackled an attractive field of research, named proteolysis, which is a widespread biochemical process that involves protein degradation, within the field of biochemistry and biomedicine. In this processes play an important role various cysteine cathepsins including cathepsin F. This enzyme differs from others cysteine cathepsins at its N-terminus. The new results contribute to better understanding of cysteine cathepsins and their role in protein degradation under physiological and pathological conditions. Moreover, the proposed project strengthened the current research on cysteine cathepsins at the Department of Biochemistry and Molecular and Structural Biology at the Jožef Stefan Institute. An important contribution to science was achieved through publications in international journals and academic activities namely, including PhD thesis (in preparation). In addition, it was an active participation of the research team in scientific meetings (lectures, posters) and lectures at foreign universities and research institutes.
Significance for the country
Research in the field of proteases is of major importance in biochemistry, molecular, cellular and structural biology since they lead to many important discoveries. Investment in this topic will generate new knowledge which will improve the quality of life. This is important for the successful integration of Slovenia in the globalization process, EU integration and sustainable development. Members of the research team already contributed substantially in this direction.
This proposal might be considered of strategic importance. Therefore, these conditions produce creative young researchers with knowledge which can be transfered to pharmaceutical companies i.e. Lek, a Sandoz company and other research laboratories and universities, as well. For the users, mainly pharmaceutical companies, the proposed research is also of oustanding importance, due to its role in several diseases. These enzymes represent an important disease-target to develop new chemotherapeutics, such as enzyme inhibitors. The research activities of the team were supported by the Slovenian Research Agency (ARRS) and pharmaceutical companies, as well. Moreover, we are also partners in European projects (FP) EU and other international projects.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
