Parkin Precipitates on Mitochondria via Aggregation and Autoubiquitination.

The loss of the E3 ligase Parkin, in a familial form of Parkinson's disease, is thought to cause the failure of both the polyubiquitination of abnormal mitochondria and the consequent induction of mitophagy, resulting in abnormal mitochondrial accumulation. However, this has not been confirmed in patient autopsy cases or animal models. More recently, the function of Parkin as a redox molecule that directly scavenges hydrogen peroxide has attracted much attention. To determine the role of Parkin as a redox molecule in the mitochondria, we overexpressed various combinations of Parkin, along with its substrates FAF1, PINK1, and ubiquitin in cell culture systems. Here, we observed that the E3 Parkin monomer was surprisingly not recruited to abnormal mitochondria but self-aggregated with or without self-ubiquitination into the inner and outer membranes, becoming insoluble. Parkin overexpression alone generated aggregates without self-ubiquitination, but it activated autophagy. These results suggest that for damaged mitochondria, the polyubiquitination of Parkin substrates on the mitochondria is not indispensable for mitophagy.

Parkinson's Disease: Exploring Different Animal Model Systems.

Disease modeling in non-human subjects is an essential part of any clinical research. To gain proper understanding of the etiology and pathophysiology of any disease, experimental models are required to replicate the disease process. Due to the huge diversity in pathophysiology and prognosis in different diseases, animal modeling is customized and specific accordingly. As in other neurodegenerative diseases, Parkinson's disease is a progressive disorder coupled with varying forms of physical and mental disabilities. The pathological hallmarks of Parkinson's disease are associated with the accumulation of misfolded protein called α-synuclein as Lewy body, and degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) area affecting the patient's motor activity. Extensive research has already been conducted regarding animal modeling of Parkinson's diseases. These include animal systems with induction of Parkinson's, either pharmacologically or via genetic manipulation. In this review, we will be summarizing and discussing some of the commonly employed Parkinson's disease animal model systems and their applications and limitations.

Academic Integrity Perceptions Among Health-Professions' Students: A Cross-Sectional Study in The Middle East.

A high level of professional integrity is expected from healthcare professionals, and literature suggests a relationship between unethical behavior of healthcare professionals and poor academic integrity behavior at medical school. While academic integrity is well researched in western countries, it is not so in the Middle East, which is characterized by different cultural values that may influence students' academic integrity conduct. We conducted a cross-sectional study among health-professions students at a university in the Middle East to assess perceptual differences on various cheating behaviors, as well as to explore the reasons underlying the cheating behavior. A validated survey instrument disseminated among first and second-year undergraduate students resulted in 211 complete responses and this data was analyzed using descriptive and inferential statistics. Pearson's Chi-square/ Fischer's exact test was applied to test the association of various factors with academic misconduct. The major determinants of academic misconduct were investigated using Binary Logistic regression model. The conducted analysis and the results showed that preceding cheating behavior was the only factor significantly associated with cheating in the university (p < 0.001). No association was found between cheating behavior and age, college/major, awareness regarding academic integrity, or perception of faculty response. The reasons provided by students for cheating behavior were mainly academic workload and pressure to get a good grade. Various suggestions are made to enhance academic integrity among health-professions students including organizing workshops and events by the university to increase awareness and create an academic integrity culture, providing peer guidance as well as emotional and social support. Supplementary information: The online version contains supplementary material available at 10.1007/s10805-022-09452-6.

Ellagic Acid Prevents α-Synuclein Spread and Mitigates Toxicity by Enhancing Autophagic Flux in an Animal Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurological disorder, pathologically characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) as well as the formation of Lewy bodies composed mainly of α-synuclein (α-syn) aggregates. It has been documented that abnormal aggregation of α-syn is one of the major causes of developing PD. In the current study, administration of ellagic acid (EA), a polyphenolic compound (10 mg/kg bodyweight), significantly decreased α-syn spreading and preserved dopaminergic neurons in a male C57BL/6 mouse model of PD. Moreover, EA altered the autophagic flux, suggesting the involvement of a restorative mechanism meditated by EA treatment. Our data support that EA could play a major role in the clearing of toxic α-syn from spreading, in addition to the canonical antioxidative role, and thus preventing dopaminergic neuronal death.