A study on the interaction of the amyloid fibrils of α-synuclein and hen egg white lysozyme with biological membranes

Alpha-synuclein (alpha-syn) aggregation and mitochondrial dysfunction are considered as two of the main factors associated with Parkinson's disease (PD). In the present investigation, the effectiveness of the amyloid fibrils obtained from alpha-syn with those of hen egg white lysozyme (HEWL), as disease-related and-unrelated proteins, to damage rat brain and rat liver mitochondria have been investigated. This was extended by looking at SH-SY5Y human neuroblastoma cells and erythrocytes, thereby investigating the significance of structural characteristics of amyloid fibrils related to their interactions with biomembranes obtained from various sources. Results presented clearly demonstrate substantial differences in the response of tested biomembranes to toxicity induced by alpha-syn/HEWL amyloid fibrils, highlighting a structure-function relationship. We found that fibrillar aggregates of alpha-syn, but not HEWL, caused a significant increase in mitochondrial ROS, loss of membrane potential, and mitochondrial swelling, in a dose-dependent manner. Toxicity was found to be more pronounced in brain mitochondria, as compared to liver mitochondria. For SH-SY5Y cells and erythrocytes, however, both alpha-syn and HEWL amyloid fibrils showed the capacity to induce toxicity. Taken together, these results may suggest selective toxicity of alpha-syn amyloid fibrils to mitochondria mediated likely by their direct interaction with the outer mitochondrial membrane, indicating a correlation between specific structural characteristics of alpha-syn fibrils and an organelle strongly implicated in PD pathology.

Automated summary

The study investigated the effects of amyloid fibrils from alpha-syn and HEWL on rat brain and liver mitochondria, showing that alpha-syn fibrils exhibited more toxicity compared to HEWL. Both types of fibrils were found to induce toxicity in SH-SY5Y cells and erythrocytes.