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Investigations into the role of DNAJ Proteins as modulators of amyloid protein aggregation

Rodríguez González, Claudio (2019) MOBN03 20182
Degree Projects in Molecular Biology
Popular Abstract
Implication of DNAJ co-chaperones in Neurodegenerative diseases

General improvements of human life conditions at different levels translate into an increasingly growing life span expectancy of the earth population. This, however comes with the cost of an increase in neurodegenerative diseases which broadly increases in frequency with age.

Most age related brain diseases such as Parkinson’s disease and Alzheimer’s disease and even some brain conditions affecting younger patients such as Huntington’s disease, share a common characteristic: the presence of protein aggregates within the brain. Proteins are a heterogeneous group of biochemical molecules with different but fundamental roles in cell life. Proteins consist of a chain of... (More)
Implication of DNAJ co-chaperones in Neurodegenerative diseases

General improvements of human life conditions at different levels translate into an increasingly growing life span expectancy of the earth population. This, however comes with the cost of an increase in neurodegenerative diseases which broadly increases in frequency with age.

Most age related brain diseases such as Parkinson’s disease and Alzheimer’s disease and even some brain conditions affecting younger patients such as Huntington’s disease, share a common characteristic: the presence of protein aggregates within the brain. Proteins are a heterogeneous group of biochemical molecules with different but fundamental roles in cell life. Proteins consist of a chain of smaller molecules called amino acids. In order to perform their role effectively, that chain of amino acids has to be folded into a specific and characteristic way. If for some reason certain proteins do not have the correct conformation, they will tend to form aggregates. Aggregation inside a research cell line can be seen as green dots in the photograph bellow.

In order to avoid excessive accumulation of proteins inside of cells, evolution has drifted towards the acquisition of a protein regulation system. This mechanism allows detection of misfolded proteins for subsequent refolding or destruction. The specific molecules largely in charge of that detection step are the so called DNAJ proteins. DNAJ family consist of more than 40 proteins which all share a J-domain, essential for their function.

Research approach
Having a better understanding of how cells regulate protein aggregation via these DNAJ proteins can be fundamental in order to design and develop a treatment for these kind of diseases. In my master project, three different approaches to the study of DNAJ proteins were carried out.

Two research lines investigate DNAJ proteins associated with Parkinson’s disease: DNAJB6 and DNAJC6. I carried out preliminary work with a Parkinson mice model overexpressing DNAJB6 and tried to generate a cellular line aiming to study the specific location and role of DNAJC6 within the cell. Although being promising projects, neither of those studies provided any novel results yet.

The third research line in which I worked, is related with Huntington’s disease. It involved the creation of 3 cell disease model lines without the expression of the DNAJ protein subject of study, DNAJA1, DNAJB1 or DNAJB6. Using two different quantification methods, it was concluded that DNAJB1 does not affect protein aggregation in our cell model, however, DNAJB6 absence increases aggregation and vice versa in the case of DNAJA1. Upon reanalysis and further confirmation of reported results, the antagonistic interaction between DNAJB6 and DNAJA1 has the potential to open new research lines targeting the design of new disease treatment approaches.

Master’s Degree Project in Molecular Biology 60 credits 2019
Department of Biology, Lund University

Supervisor: Dr. Christian Hansen
Molecular Neurobiology group, Faculty of Medicine, Department of Experimental Medical Science, Sölvegatan 19, BMC B11, Lund (Less)
Please use this url to cite or link to this publication:
author
Rodríguez González, Claudio
supervisor
organization
course
MOBN03 20182
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8995154
date added to LUP
2019-09-17 09:18:07
date last changed
2019-09-17 09:18:07
@misc{8995154,
  author       = {{Rodríguez González, Claudio}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Investigations into the role of DNAJ Proteins as modulators of amyloid protein aggregation}},
  year         = {{2019}},
}