Question

What are some diseases caused by misfolded proteins?

Short answer

Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jakob disease.

Step-by-step solution

- Understand Protein Misfolding

Protein misfolding occurs when proteins do not fold into their correct three-dimensional shape. This misfolding can disrupt their normal function and lead to disease.

- Identify Common Diseases

There are several diseases linked to protein misfolding. Some of them include Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jakob disease.

- Detailed Examples

For instance, Alzheimer's disease is associated with the misfolding of amyloid-beta and tau proteins. Parkinson's disease connects to the misfolding of alpha-synuclein proteins. Creutzfeldt-Jakob disease is linked to the misfolding of prion proteins.

Key concepts

Alzheimer's disease

Alzheimer's disease is a neurodegenerative disorder that leads to memory loss and cognitive decline. It is often considered the most common cause of dementia.
The disease is associated with two types of misfolded proteins: amyloid-beta and tau.
An accumulation of amyloid-beta forms plaques between neurons, disrupting cell communication. These plaques make it difficult for neurons to function properly.
Misfolded tau proteins result in tangles within neurons, leading to cell death and brain shrinkage.
Both the plaques and tangles contribute to the symptoms of Alzheimer's disease, like memory lapses and confusion.

Parkinson's disease

Parkinson's disease primarily affects movement. Symptoms include tremors, stiffness, and difficulty with balance and coordination.
The root of the problem is the misfolding of a protein called alpha-synuclein.
Misfolded alpha-synuclein accumulates to form Lewy bodies, which are toxic to neurons.
The neurons most affected are those in the substantia nigra, an area of the brain that regulates movement.
This loss of dopamine-producing neurons leads to the motor dysfunction typical of Parkinson's disease.

Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a rare, fatal brain disorder that deteriorates brain function. It belongs to a group of conditions known as prion diseases.
The culprit is prion proteins, which can misfold and replicate their abnormal structure.
Misfolded prion proteins accumulate in the brain, causing severe brain tissue damage.
Symptoms include rapid mental deterioration, memory loss, personality changes, and physical impairment.
CJD is unique because it can be sporadic, hereditary, or acquired, but all forms involve prion protein misfolding.

Protein misfolding

Proteins must fold into specific three-dimensional shapes to function correctly. When proteins misfold, it disrupts their normal activity and can cause diseases.
Misfolding can result from genetic mutations, environmental factors, or errors during protein synthesis.
The body usually has mechanisms to eliminate misfolded proteins, but sometimes these mechanisms fail.
Accumulation of misfolded proteins can lead to toxic effects in cells and tissues, commonly affecting the brain.
This concept is crucial for understanding various neurodegenerative disorders.

Amyloid-beta

Amyloid-beta is a protein fragment linked to Alzheimer's disease. It is formed from the cleavage of a larger protein called amyloid precursor protein (APP).
When amyloid-beta accumulates, it forms plaques between neurons in the brain.
These plaques disrupt cell communication and provoke an immune response leading to inflammation.
Inflammation caused by amyloid-beta plaques further damages neurons, contributing to the progression of Alzheimer's disease.
Targeting amyloid-beta is a major focus of research for treating and preventing Alzheimer's.

Tau proteins

Tau proteins are important for stabilizing microtubules, which are structures that support and transport materials within neurons.
In Alzheimer's disease, tau proteins become hyperphosphorylated, meaning many phosphate groups attach to them.
This abnormal modification turns tau proteins into twisted tangles within the neurons, leading to cell death.
Unlike amyloid-beta, tau tangles are found inside the neurons, disrupting their function from within.
Research on tau proteins aims to understand how to prevent or reverse these harmful tangles.

Alpha-synuclein

Alpha-synuclein is a protein found throughout the brain, but its exact function is still not completely understood.
In Parkinson's disease, alpha-synuclein proteins misfold and form aggregates known as Lewy bodies.
These Lewy bodies are toxic to neurons, particularly in the substantia nigra, leading to dopamine deficiency.
This dopamine deficiency causes the motor symptoms observed in Parkinson's disease, such as tremors and rigidity.
Understanding alpha-synuclein misfolding can help develop treatments to halt or slow down the progression of Parkinson's.

Prion proteins

Prion proteins are unique because they can cause diseases by changing their shape and inducing other prion proteins to misfold similarly.
This misfolding leads to a chain reaction, where abnormal prion proteins accumulate and cause cell damage.
Prion diseases, including Creutzfeldt-Jakob disease, are usually fatal and can affect both humans and animals.
Symptoms of prion diseases include rapid neurodegeneration, memory loss, and severe brain damage.
Research into prion proteins helps understand their unique mechanism of disease propagation and explore potential treatments.