Presenter of 1 Presentation
STRUCTURAL AND BIOCHEMICAL CHARACTERIZATION OF BRAIN DERIVED Α-SYNUCLEIN FIBRILS FROM PD AND MSA
Abstract
Aims
Parkinson’s disease (PD) and multiple system atrophy (MSA) are characterized by the accumulation of filamentous α-synuclein in the brain. However, limited studies have scrutinized the brain derived α-synuclein fibrils and examined how these differ from the fibrils generated with seeding amplification assay like real-time quaking induced conversion (RT-QuIC). Here, we characterize the structural and biochemical properties of the human α-synuclein fibrils. Also, we compare the properties between the human and RT-QuIC amplified fibrils.
Methods
We extracted α-synuclein fibrils from the PD and MSA brains and in parallel generated RT-QuIC amplified fibrils. The morphology of the fibrils was observed using transmission electron microscopy (TEM) and immunogold TEM with antibodies targeting different regions of α-synuclein. Also, biochemical characterization was performed using slot-blot with the same set of antibodies. These observations were further examined with the clinical and neuropathological information.
Results
PD α-synuclein fibrils displayed two structurally distinct TEM morphologies, which were ‘straight’ and ‘twisted’. On the other hand, MSA α-synuclein fibrils were only composed of ‘straight’ fibrils. Furthermore, immunogold antibodies showed different labelling patterns with the α-synuclein fibrils, which provided structural information about the exposed and embedded regions of the fibrils. Also using the slot-blot, we were able to identify different α-synuclein species in the PD and MSA cases.
Conclusions
PD and MSA α-synuclein fibrils showed distinct structural and biochemical characteristics. This finding might provide a further insight about the mechanism on how the α-synuclein strains associate with different synucleinopathies and the causal link to the clinical and neuropathological variability, especially in PD.