How does alpha-synuclein become misfolded?

The reason why alpha-synuclein becomes misfolded in the brain or the gut is unknown. We hypothesize that alpha-synuclein misfolding in gut and brain neurons in caused by exposure to proteins of similar structure that are contained in bacteria that reside in the mouth and gut.

Is alpha-synuclein misfolded?

Alpha-synuclein is an abundant presynaptic brain protein, misfolding, aggregation and fibrillation of which are implicated as critical factors in several neurodegenerative diseases.

What disease is caused by misfolded synuclein protein?

Parkinson’s disease belongs to a class of neurodegenerative disorders known as synucleinopathies, in which the loss of nerve cells is mainly triggered by the buildup of misfolded alpha-synuclein, a protein that is particularly abundant in the brain, where it is thought to help control neuron function and communication.

What causes build up of alpha-synuclein?

Exposure of neurons expressing endogenous levels of α-synuclein to fibrils causes formation of α-synuclein inclusions that morphologically and biochemically resemble Lewy neurites and Lewy bodies [15].

How does protein misfolding cause Parkinson disease?

Parkinson’s disease is one of a group of conditions known as “protein misfolding diseases,” because they are characterized by specific proteins becoming distorted and malfunctioning. These proteins then cluster into thread-like chains, which are toxic to other cells.

How does protein misfolding cause cystic fibrosis?

Cystic fibrosis (CF) is a disease caused by aberrant expression, or misfolding, of CFTR. Mutations affecting protein folding and function: Many genetic mutations have been associated with CF, but the impact of these mutations can be classified (class I-VI) by how they affect the expression, or folding of, CFTR.

How does the misfolding of proteins cause Alzheimer’s?

In patients with Alzheimer’s disease, misfolding of the amyloid-β protein may occur 15-20 years before the first clinical symptoms are observed. The misfolded proteins accumulate and form amyloid plaques in the brain.

What is the role of α-Synuclein in the pathology of the disease?

Therefore, the main function of α-synuclein would appear to be the control of neurotransmitter release, through effects on the SNARE complex. Recent evidence, to be discussed below, suggests that this physiological function may provide insight into the aberrant function unleashed in disease states.

What is the role of the α-Synuclein protein?

α-Synuclein localizes specifically to the nerve terminal and inhibits neurotransmitter release when over-expressed, but the knockout has a modest effect on synaptic transmission, suggesting alternative presynaptic roles.

What happens if a protein is misfolded?

Accumulation of misfolded proteins can cause disease, and unfortunately some of these diseases, known as amyloid diseases, are very common. The most prevalent one is Alzheimer’s disease, which affects about 10 percent of the adult population over sixty-five years old in North America.

What protein structure is altered in cystic fibrosis?

Cystic fibrosis occurs when the cystic fibrosis transmembrane conductance regulator (CFTR) protein is either not made correctly, or not made at all.