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Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting

Jafarieh O, Md S, Ali M, Baboota S, Sahni JK, Kumari B, et al.

Drug Dev Ind Pharm, 2015;41(10):1674-81.
PMID: 25496439 DOI: 10.3109/03639045.2014.991400

Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.

Matched MeSH terms: Parkinson Disease/drug therapy
Fulltext Edible bird's nest ameliorates oxidative stress-induced apoptosis in SH-SY5Y human neuroblastoma cells

Yew MY, Koh RY, Chye SM, Othman I, Ng KY

BMC Complement Altern Med, 2014;14:391.
PMID: 25308934 DOI: 10.1186/1472-6882-14-391

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.

Matched MeSH terms: Parkinson Disease/drug therapy
Factors associated with cognitive impairment in patients with Parkinson disease: an urban study

Rosdinom R, Fazli A, Ruzyanei NJ, Azlin B, Srijit D

Clin Ter, 2011;162(1):23-9.
PMID: 21448542

BACKGROUND AND AIMS: Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer disease. Besides motor presentations, cognitive impairment is among the other likely complications as the illness progresses. This study aimed to determine the prevalence of cognitive impairment in PD and the factors associated with the cognitive impairment.
MATERIALS AND METHODS: A cross-sectional, descriptive study was conducted on all PD patients at different stages of their illness, in two major tertiary hospitals in Malaysia with their caregivers, over a three month period in 2002. Patients' cognitive functions were tested using the Mini Mental State Examination (MMSE). Important sociodemographic data and relevant clinical information of the patients as well as caregivers' information on income, duration of care-giving, relationship with the patient, and other relevant variables were gathered. Patients' level of functioning was assessed using the Activities of Daily Living (ADL) index. Staging of illness was done based on the Hoehn and Yahr Scale.
RESULTS: Out of 115 eligible patients, 35% were in the 60-69 age group with 57% in stage 2 of illness, A total of 29% of patients experienced various degrees of cognitive impairment , with almost half (47%) in the stage 3 and 4 exhibiting MMSE scores <24. Factors which were significantly associated with impaired cognitions were race, educational level and stage of illness.
CONCLUSION: Cognitive impairment was fairly common in PD and the severity of impairment in cognition and physical functioning increased with the advancement of the illness.

Matched MeSH terms: Parkinson Disease/drug therapy
Fulltext Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson's disease

Hashim H, Azmin S, Razlan H, Yahya NW, Tan HJ, Manaf MR, et al.

PLoS One, 2014;9(11):e112330.
PMID: 25411976 DOI: 10.1371/journal.pone.0112330

BACKGROUND: Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.
METHODS: A prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa 'onset' time and ON-duration were recorded.
RESULTS: Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.
CONCLUSIONS: H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02112812.

Matched MeSH terms: Parkinson Disease/drug therapy*
Butyrylcholinesterase: A Multifaceted Pharmacological Target and Tool

Ha ZY, Mathew S, Yeong KY

Curr Protein Pept Sci, 2020;21(1):99-109.
PMID: 31702488 DOI: 10.2174/1389203720666191107094949

Butyrylcholinesterase is a serine hydrolase that catalyzes the hydrolysis of esters in the body. Unlike its sister enzyme acetylcholinesterase, butyrylcholinesterase has a broad substrate scope and lower acetylcholine catalytic efficiency. The difference in tissue distribution and inhibitor sensitivity also points to its involvement external to cholinergic neurotransmission. Initial studies on butyrylcholinesterase showed that the inhibition of the enzyme led to the increment of brain acetylcholine levels. Further gene knockout studies suggested its involvement in the regulation of amyloid-beta, a brain pathogenic protein. Thus, it is an interesting target for neurological disorders such as Alzheimer's disease. The substrate scope of butyrylcholinesterase was recently found to include cocaine, as well as ghrelin, the "hunger hormone". These findings led to the development of recombinant butyrylcholinesterase mutants and viral gene therapy to combat cocaine addiction, along with in-depth studies on the significance of butyrylcholinesterase in obesity. It is observed that the pharmacological impact of butyrylcholinesterase increased in tandem with each reported finding. Not only is the enzyme now considered an important pharmacological target, it is also becoming an important tool to study the biological pathways in various diseases. Here, we review and summarize the biochemical properties of butyrylcholinesterase and its roles, as a cholinergic neurotransmitter, in various diseases, particularly neurodegenerative disorders.

Matched MeSH terms: Parkinson Disease/drug therapy*
Fulltext Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment

Shao YM, Ma X, Paira P, Tan A, Herr DR, Lim KL, et al.

PLoS One, 2018;13(1):e0188212.
PMID: 29304113 DOI: 10.1371/journal.pone.0188212

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).

Matched MeSH terms: Parkinson Disease/drug therapy*
Pharmacological evaluation of vanillic acid in rotenone-induced Parkinson's disease rat model

Sharma N, Khurana N, Muthuraman A, Utreja P

Eur J Pharmacol, 2021 Jul 15;903:174112.
PMID: 33901458 DOI: 10.1016/j.ejphar.2021.174112

In the present study, we investigated the anti-Parkinson's effect of vanillic acid (VA) (12 mg/kg, 25 mg/kg, 50 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson's disease (PD) in rats. The continuous administration of rotenone for 35 days resulted in rigidity in muscles, catalepsy, and decrease in locomotor activity, body weight, and rearing behaviour along with the generation of oxidative stress in the brain (rise in the TBARS, and SAG level and reduced CAT, and GSH levels). Co-treatment of VA and levodopa-carbidopa (100 mg/kg + 25 mg/kg p.o.) lead to a significant (P drug treated animals as compared to rotenone treated group. Histopathological evaluation showed a high number of eosinophilic lesions in the rotenone group which were found to be very less in the VA co-treated group. The study thus proved that co-treatment of VA and levodopa-carbidopa, significantly protected the brain from neuronal damage due to oxidative stress and attenuated the motor defects indicating the possible therapeutic potential of VA as a neuroprotective in PD.

Matched MeSH terms: Parkinson Disease/drug therapy*