egg-white and Parkinson-Disease

Alpha-synuclein (α-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 α-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 α-syn/HEWL amyloid fibrils, highlighting a structure-function relationship. We found that fibrillar aggregates of α-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 α-syn and HEWL amyloid fibrils showed the capacity to induce toxicity. Taken together, these results may suggest selective toxicity of α-syn amyloid fibrils to mitochondria mediated likely by their direct interaction with the outer mitochondrial membrane, indicating a correlation between specific structural characteristics of α-syn fibrils and an organelle strongly implicated in PD pathology.

Topics: alpha-Synuclein; Amyloid; Animals; Brain; Cell Line, Tumor; Cell Membrane; Chickens; Egg White; Erythrocytes; Humans; Membrane Potential, Mitochondrial; Mitochondria, Liver; Muramidase; Parkinson Disease; Rats; Structure-Activity Relationship

Patients with chronically implanted deep brain stimulator (DBS) electrodes can encounter complications requiring hardware removal. We assessed the safety and efficacy of using implanted DBS electrodes to create a therapeutic lesion before their removal.. Revision or removal of the DBS electrodes was required in two patients who had previously undergone DBS implantation. We conducted a series of in vitro experiments to confirm that the DBS electrodes could be used to generate radiofrequency lesions and to assess the relationship between radiofrequency parameters and lesion size. With this information, and with the approval of the hospital ethical review board, implanted electrodes were used to create incremental radiofrequency lesions in the thalamus in one patient and in the subthalamic nucleus in another. The procedures were performed under local anesthesia with contiguous contacts of the DBS lead connected to the active and reference sites of the RF generator to create a bipolar lesion.. A 51-year-old man with essential tremor and a thalamic DBS required repeated battery changes secondary to tolerance and high voltage demands. Rather than replacing the battery, a radiofrequency thalamotomy was performed by using the existing left DBS electrode. At the 6-month follow-up examination, successful lesioning provided near complete tremor control. A second patient, a 50-year-old man with Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation, developed skin erosion over the DBS hardware. A subthalamic nucleus lesion was made through the right DBS electrode. Lesion position and size were confirmed with magnetic resonance imaging.. Lesions can be made through chronically implanted DBS electrodes in a safe, graded fashion and can produce therapeutic benefit.

Topics: Device Removal; Egg White; Electric Stimulation Therapy; Electrodes; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Radiosurgery; Subthalamic Nucleus; Thalamus; Treatment Outcome; Tremor