الفهرس 
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Abstract
Parkinson’s disease is a chronic neurodegenerative movement disorder pathologically characterized by the deficiency of brain dopamine content and selective degeneration of substantia nigra’s dopaminergic neurons. Various pathogenic mechanisms have been associated with nigral cell death, including oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate excitotoxicity and impairment in protein degradation pathways, such as the ubiquitinproteasome system. Mitochondria is a vital organelle which has a critical role in energy production, apoptosis, the tricarboxylic acid cycle, calcium homeostasis and also regulate cell growth and cell cycle. Mitochondrial quality control is an important process that maintains mitochondrial homeostasis and involves multi-level regulatory mechanisms, such as mitophagy, mitochondrial fission and fusion, mitochondrial energy metabolism, mitochondrial antioxidant system, and mitochondrial respiratory chain. Mitochondrial biogenesis is a common pathway involved in pathogenesis of Parkinson’s disease in which parkin inactivation leads to accumulation of the PARIS and repression of proliferatoractivated receptor gamma coactivator-1-alpha (PGC-1α) promoter activity leading to prevention of mitochondrial biogenesis resulting in dopamine cell loss. The parkin-interacting substrate (PARIS) is a 644 amino acid protein that contains a Kruppel-associated box (KRAB) at its Nterminus and a C2HC/C2H2 type zinc finger at its C-terminus. The cellular levels of parkin –interacting substance (PARIS) is regulated by phosphatase and tensin homolog (PTEN)‐induced kinase 1 (PINK1) mediated phosphorylation and parkin dependent ubiquitination. Therefore, it links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival. Sumoylation that is a post-translational modification involved in various cellular processes, such as nuclear – cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle. SUMOtargeted ubiquitin ligase ring finger protein (RNF4) which is a poly- SUMO-specific E3 ubiquitin ligase, is associated with protein degradation and DNA damage repair, also it mediates PARIS sumoylation that induced its ubiquitination and subsequent proteasomal degradation. Lauric acid (LA) is a member group of medium-chain fatty acids (MCFA) and contains 12 carbon atoms. It is found in a wide variety of foods including fruits, seeds, human milk, and constitutes about half of the fatty acid content in laurel oil and coconut oil. LA has been recently drawn attention due to its role in neuro-behavioral modulation, besides its beneficial effects as a potent antiinflammatory, anti-cancer and antioxidant agent. However, its effects on mitochondrial biogenesis regulation have not been fully elucidated. The aim of this work was to investigate the modulatory effects of LA on some regulators of mitochondrial biogenesis in a rat model of rotenone-induced PD in order to provide a new mechanistic insight and to launch promising avenues for the potential use of LA as a neuroprotective agent in PD. Experimental design: After acclimatization for one week; rats were randomly divided into four equal groups of 15 rats each as follows: group I (control group): Rats were received vehicle of 1% DMSO at a dose of 0.1 mL/100 g/day; S.C for 3 weeks. group II (LA-treated group): Rats were received only LA via oral gavage at a dose of 50 mg/kg/day for 3 weeks. group III (rotenone-administered group): Rats were received eleven S.C injections of rotenone every other day at a dose of 1.5 mg/kg dissolved in 1% DMSO for 3 weeks. group IV (rotenone and LA-treated group): Rats were received both rotenone (S.C injections; every other day at a dose of 1.5 mg/kg dissolved in 1% DMSO for 3 weeks) and LA via oral gavage at a dose of 50 mg/kg/day; daily for 3 weeks and 1 h before rotenone administration on the days of rotenone injection. II- Methods: -At the end of the experiment on the 21st day: Rats were subjected to neurobehavioral assessment by the following tests: catalepsy test, grip Strength test, rearing test, apomorphine test. Tissue sampling: Rats were sacrificed under anesthesia, brains were immediately dissected carefully, washed with ice cold saline to remove extraneous materials. The excess saline was blotted by pieces of filter paper. The brain tissues were chilled on ice and divided into two halves. A- The first half was wrapped in aluminum foil and stored at – 80°C till used for preparation of brain tissue homogenates. B-The second half was kept in 10% formalin solution for histopathological study. Biochemical assay: 1. Assessment of ring finger protein 4 (RNF4) relative gene expression level in the brain tissues by quantitative realtime PCR (RT-PCR). 2. Estimation of parkin-interacting substance (PARIS) levels, in the brain tissue homogenates by ELISA. 3. Protein carbonyl content (PCC) assay in the brain tissue homogenates by spectrophotometry. 4. Glutathione peroxidase (GPx) enzymatic activity in the brain tissue homogenates by spectrophotometry. Results of the present study revealed the following: There were statistically significant differences in descent latency time, grip strength and number of rears /5 min among all groups. There was a statistically significant increase in descent latency time in rotenone-administered group (group III) compared to other studied groups while a statistically significant decrease in grip strength and number of rears /5 min in rotenone-administered group (group III) was found compared to other studied groups. There were statistically significant differences in brain tissue levels of RNF4, PARIS, PCC and GPx activity among all groups. There was a statistically significant brain tissue levels of RNF4 and GPx activity in rotenone-administered group (group III) compared to other studied groups while a statistically significant increase in brain tissue levels of PARIS and PCC in rotenone-administered group (group III) was found compared to other studied groups. Moreover, lauric acid significantly increased the brain tissue levels of RNF4 and GPx activity while, it decreased the brain tissue levels of PARIS and PCC. Also, brain tissue levels of RNF4 showed a significant positive correlation with brain tissue GPx among all groups. Meanwhile RNF4 levels show a significant negative correlation with brain tissue levels of PARIS and PCC among all groups. Also, histopathological study confirmed the biochemical findings brain of PD group group III showed marked inflammation, astrocytosis and necrosis compared to control groups (group I and II). Which were characterized by normal brain histology with absent astrocytosis and neuronal necrosis. While, LA-treated rats (group IV) showed less histopathological abnormalities including marked improvement of astrocytosis and necrosis compared to PD.