What diseases are caused by protein aggregation?
Protein aggregation diseases include Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, dementia with Lewy bodies, frontotemporal dementia and Huntington’s disease. Moreover, amyloid transthyretin cardiomyopathy and type-2 diabetes are increasingly recognized as protein aggregation diseases.
What are polyglutamine disorders?
Polyglutamine diseases are a family of neurodegenerative conditions that each derive from a CAG triplet repeat expansion in a specific gene. This produces a pathogenic protein that contains a critically expanded tract of glutamines.
What is polyglutamine aggregation?
Expansion of polyglutamine (polyQ) tracts in proteins results in protein aggregation and is associated with cell death in at least nine neurodegenerative diseases. Disease age of onset is correlated with the polyQ insert length above a critical value of 35–40 glutamines.
Does protein aggregation cause neurodegenerative disease?
Protein aggregation is a common characteristic of many neurodegenerative diseases. The aggregates and/or oligomers appear to be toxic, causing injury or death to cells. In general, the greater the degree of aggregation, the greater is the severity of disease.
What is polyglutamine expansion?
Polyglutamine diseases are a large group of inherited neurodegenerative disorders caused by the expansion of the CAG trinucleotide, encoding the amino acid glutamine, in the coding region of different and functionally unrelated genes (Zoghbi and Orr, 2000).
What is a polyQ stretch?
Polyglutaminopathies are a family of diseases characterized by CAG trinucleotide expansions in the coding regions of at least nine unrelated genes, resulting in proteins with an abnormally long polyglutamine (polyQ) stretch, which have a high aggregation propensity.
What does protein aggregation cause?
Protein misfolding and aggregation is the common cause and pathological mechanism of neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), PD, and Huntington’s disease (HD).
How does protein aggregation lead to Alzheimer’s disease?
Alzheimer’s disease, for example, develops because the A-beta and tau proteins aggregate, which leads to neuronal dysfunction and cell death. According to Alzheimer Forschung Initiative e. V., approximately 1.2 million people suffer from this disease only in Germany. The risk to fall ill grows with increasing age.
Which of these protein misfolding and aggregation is linked to Alzheimer’s disease?
Alzheimer’s disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain.