An oligomer is a molecule consisting of several intermediate units derived from lower molecular mass molecules. At times, proteins can be oligomerized, meaning that they contain more than one polypeptide chain. With oligomers being connected to Parkinson’s disease (PD), there has been an increase in research targeted at proteins found in brain neurons.
Here at StressMarq Biosciences Inc., we have launched dopamine-stabilized alpha-synuclein oligomers. These proteins are useful in studying the neurotoxic nature of oligomers and their contribution to neurodegenerative ailments.
What Role Do Alpha-Synuclein Oligomers Have in Disease?
Oligomerized intermediaries are responsible for the aggregation of alpha-synuclein from monomers into amyloid fibrils. Monomers are basically molecules that bond to each other to form a polymer. Amyloid fibrils, on the other hand, refer to proteins that have misfolded and accumulated together. This process, termed as protein aggregation, is known to be a toxic disease-causing mechanism.
Oligomers are, therefore, directly connected to the process that makes otherwise harmless alpha-synuclein proteins harmful to brain tissue. Studying these molecules may lead to the development of a biochemical test that can make it possible to detect Parkinson’s disease early. So far, the disease can only be diagnosed once it has begun damaging the brain tissue.
Detection of alpha-synuclein oligomers in the cerebrospinal fluid before manifestation would be an early diagnosis. In that way, therapies to combat PD would be administered early enough to prevent further cellular damage.
How are Alpha-Synuclein Oligomers Stabilized?
One challenge to alpha-synuclein oligomers research is the fact that oligomers are metastable. This means that over time, they lose their stability and dissociate. In such a case, studying them in their original form becomes limited. However, these molecules can be stabilized using formaldehyde (FA).
Formaldehyde acts as an amine-reactive cross-linker and can stabilize synuclein protein oligomers without affecting their size and overall structure. Stabilizing oligomers is useful in research targeting Multiple System Atrophy (MSA), Dementia with Lewy Bodies, and Parkinson’s disease. This is because oligomers have been observed in the brain tissue of patients suffering from these three synucleinopathy diseases. They’re also suspected to be the possible cause of toxicity found in the diseased brain.
Studies have shown that alpha oligomers that have been incubated with concentrations of FA do not dissociate when boiled in Sodium Dodecyl Sulfate (SDS). SDS is a detergent used to denature proteins. This is done before SDS-PAGE, a method used to separate proteins.
Understanding the Structure of Alpha-Synuclein Oligomers
Alpha-synuclein has many oligomeric forms. Certain types of these oligomers are involved in the aggregation of proteins. Observing their features and how they relate to other amyloid species provides further insight into protein misfolding. Since misfolding of proteins plays a central role in many diseases, this is important to pathological sciences.
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