100% satisfaction guarantee Immediately available after payment Both online and in PDF No strings attached
logo-home
Previously searched by you
Previously searched by you
logo
Summary Molecular Principles of Brain Disorders: NEURODEGENERATION CA$15.23   Add to cart
Quickly navigate to
Preview
  2.  
  3. Vrije Universiteit Amsterdam (VU)
  4.  
  5. Molecular Principles of Brain Disorders

Summary

Summary Molecular Principles of Brain Disorders: NEURODEGENERATION

2 reviews
 40 views  1 purchase
  • Course
  • Molecular Principles of Brain Disorders
  • Institution
  • Vrije Universiteit Amsterdam (VU)

I passed the exam with an 8.5! Note: - This summary only contains the part about neurodegenerative diseases - The lecture slides on psychiatric diseases are sufficient to learn for this exam - the summary is very extensive and you should start learning early on!

Preview 4 out of 129  pages

Document information

  • December 29, 2023
  • 129
  • 2023/2024
  • Summary

Subjects

  • molecular principles
  • neuroscience
  • brain disorders
  • biomedical sciences
  • biomedische wetenschappen
  • neurodegenerative diseases

Written for

  • Vrije Universiteit Amsterdam (VU)
  • Biomedical Sciences
  • Molecular Principles of Brain Disorders
All documents for this subject (3)

2  reviews

review-writer-avatar

By: suzanne22 • 6 days ago

review-writer-avatar

By: Dana1234 • 2 months ago

Seller

avatar-seller
lvd26

Reviews received

Content preview

Molecular Principles of: Neurodegenerative Diseases

Lecture 4, general Mechanisms in Neurodegeneration
Learning objectives:
In relation to neurodegenerative disease, the student:
• Understands and can describe the involvement of protein misfolding/aggregation
(oligomers/fibrils, localisation, aetiology)
• Understands and can describe key pathways in protein quality control
(chaperones, Ubiquitin proteasome and autophagy)
• Understands the mechanism of proteostatic stress responses
(Heatshock response, unfolded protein response)
• Understands the involvement of the neuroinflammatory response

Neurodegeneration= loss of brain cells




- You can see it by the eye
- How do we get from a healthy brain to a brain with a disorder?




First described Alzheimer's disease patient → loss of memory and orientation in time

What will be discussed coming weeks:
- Common themes Prion disease
- Specific disease examples Amyotrophic lateral sclerosis
Alzheimer’s disease - Aetiology
Frontotemporal dementia - Genetics
Huntington’s disease - Pathogenic pathways
Parkinson’s disease - Disease models
Lewy Body dementia - Therapeutic strategies

,Neurodegenerative disorders




- The arrows point to the brain region that is primarily affected by a particular
neurodegenerative disease.
- What is common in all these diseases is that they have protein occlusions, but the
protein might be different as may the area where the occlusions occur.

Protein aggregates




If a protein wants to function it has to fold in a specific way. When they are misfolded the
beta sheets are exposed which are sticky, these can stick to other misfolded proteins with
beta-sheet exposures. This ends up as a very large rigid structure which hardly can come
apart.

,Alzheimer already knew and observed this phenoma




Protein aggregates
1. Loss of function (because misfolded proteins can’t function anymore→ this may
cause a different phenotype of a cell)
2. Gain of toxic function (e.g., they can damage membranes and organelles)
→Therefore: protein quality control

Protein synthesis




mRNA is translated into proteins by ribosomes in the cytosol or the ER. The ER is a
membranous compartment to which ribosomes are attached. When a protein is synthesized
in the ER is particularly done for proteins that need to be packaged in a membrane (also
transmembrane proteins are synthesized here)
In both compartments, after the synthesis of proteins, you want that protein to have a
particular functional conformation.

, Protein folding and quality control




Proteins can only function when they have a specific conformation. However, this goes wrong
all the time, 30% of protein synthesis goes wrong even in healthy young humans.
Chaperones bind to misfolded proteins and keep them in a folding-competent state. In
addition, when a chaperone is bound, the protein can’t bind to another protein and thus
cannot aggregate.

Chaperones (Heat-shock proteins, HSP): Chaperone facilitate protein folding and refolding by
keeping proteins in “a folding-competent state”




Two classes:
ATP dependent
- Hsp90
- Hsp70
- Hsp60
ATP independent
- Small Hsp

The Hsp70 cycle
Binding and release of substrate
(unfolded protein) is dependent on:
- co-chaperone
- ATP

There are two stages of the chaperone,
an ATP-bound state and ADP bound
state. Upon binding of ATP, it gets a
different structure, an open chaperone
state, in this state the misfolded protein
can bind. Then when ATP hydrolyzes
the chaperone closes and the misfolded
protein is trapped and bound to the
chaperone.

The benefits of buying summaries with Stuvia:

Guaranteed quality through customer reviews

Guaranteed quality through customer reviews

Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.

Quick and easy check-out

Quick and easy check-out

You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.

Focus on what matters

Focus on what matters

Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!

Frequently asked questions

What do I get when I buy this document?

You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.

Satisfaction guarantee: how does it work?

Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.

Who am I buying these notes from?

Stuvia is a marketplace, so you are not buying this document from us, but from seller lvd26. Stuvia facilitates payment to the seller.

Will I be stuck with a subscription?

No, you only buy these notes for CA$15.23. You're not tied to anything after your purchase.

Can Stuvia be trusted?

4.6 stars on Google & Trustpilot (+1000 reviews)

64438 documents were sold in the last 30 days

Founded in 2010, the go-to place to buy study notes for 14 years now

Start selling
CA$15.23  1x  sold
  • (2)
  Add to cart