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Understanding the role of the co-chaperone Auxilin in α -synuclein aggregation

Lahiri, Trisha (2018) MOBN03 20172
Degree Projects in Molecular Biology
Popular Abstract
Can co-chaperone proteins help against Parkinson’s Disease ?

Our cells have assigned proteins called ‘chaperone’ and their helper ‘co-chaperone proteins that work extensively to regulate and maintain the protein structure in our cells. However, proteins like α-synuclein manage to clump together in nerve cells and are believed to acquire toxic characteristics that contribute to the death and damage of brain cells. In this study we focused on studying a specific co-chaperone protein which revealed its important role in protecting the nerve cells from the clumping of the toxic protein, that is usually implicated in neurodegenerative disorders like Parkinson’s disease (PD).

PD is the second most common neurodegenerative disorder. Primary... (More)
Can co-chaperone proteins help against Parkinson’s Disease ?

Our cells have assigned proteins called ‘chaperone’ and their helper ‘co-chaperone proteins that work extensively to regulate and maintain the protein structure in our cells. However, proteins like α-synuclein manage to clump together in nerve cells and are believed to acquire toxic characteristics that contribute to the death and damage of brain cells. In this study we focused on studying a specific co-chaperone protein which revealed its important role in protecting the nerve cells from the clumping of the toxic protein, that is usually implicated in neurodegenerative disorders like Parkinson’s disease (PD).

PD is the second most common neurodegenerative disorder. Primary symptoms of this disease are uncontrollable shaking and rigidity of limbs, making it difficult for the patients to move around, and lead a normal life. A protein found in neurons called α-synuclein can aggregate into clumps of protein which goes into larger protein rich clumps called Lewy bodies (LBs). It is known that α-synuclein is associated with progression of Parkinson’s Disease.

All neurons express protein that helps in folding of other proteins called chaperone proteins. Chaperone proteins along with its versatile ‘sidekick’ called co-chaperone proteins regulate and maintain the correct structure of protein, and even discard the toxic proteins. We focus our study on a particular co-chaperone protein that is exclusively found in the nerve cell endings and is known to be involved in the protein recycling and maintenance at the nerve cells. The gene that leads to this co-chaperone expression is linked to PD in such a way that mutations resulting in loss of protein expression, leads to PD early in life. Coincidently, the villainous toxic protein, α-synuclein is also usually found in similar locations and are known to interact with proteins involved in similar pathways like the co-chaperone protein. This made us interested in studying this sidekick protein and investigate its role in the aggregation of α-synuclein.

In our study, we found that the cells with loss of one particular co-chaperone showed a greater number of clumped α-synuclein as well as a higher cell death when compared to the cells with normal expression of this co-chaperone. Additionally, we also found that the clumped α-synuclein found in these cells had attained large faulty structures, that could have lent them the toxic characteristics which would hinder the normal functioning of cells. We were also interested in investigating the location of this co-chaperone protein, when there is an abundance of α-synuclein by tagging the protein as well as using fluorescent antibodies targeted to the protein. However, we realised that we were unsuccessful in attaching the tag to the protein, and additional experiments provided us with futile and inconclusive results.

Our study suggests that absence of one particular co-chaperone accelerates the α-synuclein aggregation, and thus the progression of PD. We need more studies focusing this ‘dark horse’ co-chaperone protein, to fully understand its interaction with α-synuclein and to paint a complete picture of its contribution in protecting the cells from the PD. This study further cemented the protective role of a co-chaperone protein, and this is another stepping stone to the idea of co-chaperones as potential therapeutic targets for the neurodegenerative diseases like PD.
Master’s Degree Project in Molecular Biology specialisation in Molecular Genetics and Biotechnology ,60 credits (2018)

Department of Biology, Lund University
Advisor: Christian Hansen (Less)
Please use this url to cite or link to this publication:
author
Lahiri, Trisha
supervisor
organization
course
MOBN03 20172
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8960287
date added to LUP
2018-10-15 16:23:08
date last changed
2018-10-16 08:31:59
@misc{8960287,
  author       = {{Lahiri, Trisha}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Understanding the role of the co-chaperone Auxilin in α -synuclein aggregation}},
  year         = {{2018}},
}