scholarly journals Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Amira Mohammed Ali ◽  
Hiroshi Kunugi

The vast increase of world’s aging populations is associated with increased risk of age-related neurodegenerative diseases such as Parkinson’s disease (PD). PD is a widespread disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra, which encompasses a wide range of debilitating motor, emotional, cognitive, and physical symptoms. PD threatens the quality of life of millions of patients and their families. Additionally, public welfare and healthcare systems are burdened with its high cost of care. Available treatments provide only a symptomatic relief and produce a trail of noxious side effects, which increase noncompliance. Hence, researchers have recently focused on the use of nutraceuticals as safe adjunctive treatments of PD to limit its progress and associated damages in affected groups. Propolis is a common product of the beehive, which possesses a large number of therapeutic properties. Royal jelly (RJ) is a bee product that is fed to bee queens during their entire life, and it contributes to their high physical fitness, fertility, and long lifespan. Evidence suggests that propolis and RJ can promote health by preventing the occurrence of age-related debilitating diseases. Therefore, they have been used to treat various serious disorders such as diabetes mellitus, cardiovascular diseases, and cancer. Some evolving studies used these bee products to treat PD in animal models. However, a clear understanding of the collective effect of propolis and RJ as well as their mechanism of action in PD is lacking. This review evaluates the available literature for the effects of propolis and RJ on PD. Whenever possible, it elaborates on the underlying mechanisms through which they function in this disorder and offers insights for fruitful use of bee products in future clinical trials.

2020 ◽  
Author(s):  
Megan M. Senchuk ◽  
Jeremy M. Van Raamsdonk ◽  
Darren J. Moore

AbstractBackgroundMutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of late-onset, familial Parkinson’s disease (PD), and LRRK2 variants are associated with increased risk for sporadic PD. While advanced age represents the strongest risk factor for disease development, it remains unclear how different age-related pathways interact to regulate LRRK2-driven late-onset PD.FindingsIn this study, we employ a C.elegans model expressing PD-linked G2019S LRRK2 to examine the interplay between age-related pathways and LRRK2-induced dopaminergic neurodegeneration. We find that multiple genetic pathways that regulate lifespan extension can provide robust neuroprotection against mutant LRRK2. However, the level of neuroprotection does not strictly correlate with the magnitude of lifespan extension, suggesting that lifespan can be experimentally dissociated from neuroprotection. Using tissue-specific RNAi, we demonstrate that lifespan-regulating pathways, including insulin/IGF-1 signaling, TOR, and mitochondrial respiration, can be directly manipulated in neurons to mediate neuroprotection. We extend this finding for AGE-1/PI3K, where pan-neuronal versus dopaminergic neuronal restoration of AGE-1 reveals both cell-autonomous and non-cell-autonomous neuroprotective mechanisms downstream of insulin signaling.ConclusionsOur data demonstrate the importance of distinct lifespan-regulating pathways in the pathogenesis of LRRK2-linked PD, and suggest that extended longevity is broadly neuroprotective via the actions of these pathways at least in part within neurons. This study further highlights the complex interplay that occurs between cells and tissues during organismal aging and disease manifestation.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Po-Yu Jay Chen ◽  
Lei Wan ◽  
Jung-Nien Lai ◽  
Chih Sheng Chen ◽  
Jamie Jiin-Yi Chen ◽  
...  

Abstract Background This study aimed to investigate the risk of Parkinson’s disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. Methods A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. Result After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16–1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13–1.80) and male (aHR = 1.28, 95% CI = 1.05–1.57) patients, aged more than 60 years (60–69: aHR = 1.51, 95% CI = 1.09–2.09, 70–79: aHR = 1.30, 95% CI = 1.05–1.60; 80–100: aHR = 1.40, 95% CI = 1.01–1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20–1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22–2.33), diabetes (aHR = 1.41, 95% CI = 1.12–1.78) and hypertension (aHR = 1.36, 95% CI = 1.15–1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19–1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11–1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). Conclusions Patients with AMD may exhibit a higher risk of PD than those without AMD.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S838-S838
Author(s):  
Su Jeong Kim ◽  
Anjali Devgan ◽  
Hemal H Mehta ◽  
Pinchas Cohen

Abstract Mitochondrial DNA (mtDNA) variants are associated with a wide range of diseases of aging, from diabetes to Alzheimer’s, as well as with longevity itself. However, to date, little work has thoroughly examined the functional roles of mtDNA variants in such age-related diseases or the therapeutic potential of mitochondrial-derived peptides (MDPs) in these conditions. Our lab hypothesizes that mtDNA SNPs could affect MDPs, and we recently showed that a mtDNA SNP is associated with reduced circulating levels of an MDP called humanin and with cognitive decline. How other mtDNA SNPs affect MDPs and disease risk has yet to be analyzed. Remarkably, a recent paper showed a mtDNA SNP (m.2158 T&gt;C) reduces the risk of Parkinson’s disease (PD). Of note, this SNP changes lysine (K) 4 to arginine (R) of a MDP called SHLP2, which is encoded by the 16S rRNA region of the mtDNA. SHLP2 acts as a neuroprotective factor and as a metabolic regulator. We hypothesized that K4R SHLP2 – produced by individuals who carry mtDNA m.2158 T&gt;C – is a protective factor for Parkinson’s disease. Cycloheximide-treated pulse-chase experiments additionally showed that K4R SHLP2 is more stable than WT SHLP2. WT SHLP2 has a polyubiquitination whereas K4R SHLP2 diminish the polyubiquitination. K4R SHLP2 more potently inhibits PD toxin (MPP+) induced apoptosis in neuronal cells. K4R SHLP2 reverse the mitochondrial membrane potential loss and mitochondria respiration defect in TFAM heterozygous knockout MEFs. Altogether, SHLP2 has the therapeutic potential as a precision medicine in PD.


2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Marco André Cardoso ◽  
Bassam Felipe Mogharbel ◽  
Ana Carolina Irioda ◽  
Priscila Elias Ferreira Stricker ◽  
Robson Camilotti Slompo ◽  
...  

Abstract Background Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. Levodopa (L-DOPA) remains the standard gold drug available for the treatment of PD. Curcumin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anti-amyloid, antitumor properties. Copolymers composed of poly(ethylene oxide) (PEO) and biodegradable polyesters like poly(ε-caprolactone) (PCL) that can self-assemble into nanoparticles (NP). This study describes the development of NH2-PEO-PCL diblock copolymer positively charged and modified by the addition of glutathione (GSH) on the outer surface, resulting in a synergistic delivery of L-DOPA and curcumin that would be able to pass the blood-brain barrier. Methods The NH2-PEO-PCL nanoparticles suspensions were prepared using a nanoprecipitation and solvent displacement method and were coated with GSH. NP was submitted to various characterizations assays, and to ensure the bioavailability, Vero and PC12 cells were treated with various concentrations of the loaded and unloaded NP to observe cytotoxicity. Results NP has successfully loaded L-DOPA and curcumin was stable after freeze-drying, capable of advancing into in vitro toxicity testing. After being treated up to 72 hours of various concentrations of L-DOPA and curcumin loaded NP Vero and PC12 cells, the viability of the treated cells maintained a high percentage indicating that the NPs are biocompatible. Conclusions NP consisting of NH2-PEO-PCL have been characterized as potential formulations for brain delivery of L-DOPA and curcumin, and obtained results also indicate that the developed biodegradable nanomicelles were blood compatible, presented low cytotoxicity even in longer exposure times.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Madison E. Hoes ◽  
Anastazja M. Gorecki ◽  
Frances Theunissen ◽  
Abigail L. Pfaff ◽  
...  

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.


2021 ◽  
pp. 1-11
Author(s):  
Lisa Damron ◽  
Irene Litvan ◽  
Ece Bayram ◽  
Sarah Berk ◽  
Bernadette Siddiqi ◽  
...  

Background: Hispanics are under-represented in Parkinson’s disease (PD) research despite the importance of diversity for results to apply to a wide range of patients. Objective: To investigate the perspective of Hispanic persons with Parkinson disease (PWP) regarding awareness, interest, and barriers to participation in research. Methods: We developed and administered a survey and qualitative interview in English and Spanish. For the survey, 62 Hispanic and 38 non-Hispanic PWP linked to a tertiary center were recruited in Arizona. For interviews, 20 Hispanic PWP, 20 caregivers, and six physicians providing service to Hispanic PWP in the community were recruited in California. Survey responses of Hispanic and non-Hispanic PWP were compared. Major survey themes were identified by applying grounded theory and open coding. Results: The survey found roughly half (Q1 54%, Q2 55%) of Hispanic PWP linked to a tertiary center knew about research; there was unawareness among community Hispanic PWP. Most preferred having physician recommendations for research participation and were willing to participate. Hispanics preferred teams who speak their native language and include family. Research engagement, PD knowledge, role of family, living with PD, PD care, pre-diagnosis/diagnosis emerged as themes from the interview. Conclusion: Barriers exist for participation of Hispanic PWP in research, primarily lack of awareness of PD research opportunities. Educating physicians of the need to encourage research participation of Hispanic PWP can address this. Physicians need to be aware of ongoing research and should not assume PWP disinterest. Including family members and providing research opportunities in their native language can increase research recruitment.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kelly B. Menees ◽  
Rachael H. Earls ◽  
Jaegwon Chung ◽  
Janna Jernigan ◽  
Nikolay M. Filipov ◽  
...  

Abstract Background Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood. Results Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson’s disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis. Conclusions This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson’s disease, where immune dysfunction is implicated in their etiology.


2020 ◽  
Vol 35 (6) ◽  
pp. 871-871
Author(s):  
Ryan J ◽  
Kreiner D ◽  
Gontkovsky S ◽  
Paolo A

Abstract Objective Research has identified common genetic influences on handedness and neurological/mental health phenotypes. It also has been shown there may be increased risk for development of neurological disorders/diseases among individuals naturally left-handed or demonstrating non-right-hand preference. This investigation examined prevalence of right-handed versus non-right-handed individuals with Parkinson’s disease (PD) compared to controls. Method Participants were 264 patients with PD (mean age = 69.83 years) and 256 control volunteers (mean age = 71.42 years). Mean Dementia Rating Scale composites for the groups were 123.68 and 136.00, respectively. Participants self-identified their dominant hand for writing and usage was confirmed during the session. Results Proportions of non-right- and right-handed controls (7.0% and 93.0%) versus individuals with PD (6.8% and 93.2%) did not differ. Changes in proportions of non-right- and right-handedness across age ranges were not significant for controls or patients. There was a trend for a larger proportion of women (55.9%) versus men among controls (44.1%), □ 2 (1) = 3.29, p &lt; .10; whereas, the proportion of men (64.4%) with PD was larger than that of women. (35.6%), □ 2 (1) = 21.31, p &lt; .001. For controls and patients, non-right and right handedness gender proportions were similar. Conclusions This study is the first to assess handedness prevalence rates in PD. Results suggest prevalence of non-right handedness is similar in PD and healthy individuals and does not appear to differ markedly by gender or with advancing age. The occurrence of a trend for a larger proportion of women than men among controls is consistent with census-based statistics.


Cephalalgia ◽  
2016 ◽  
Vol 36 (14) ◽  
pp. 1316-1323 ◽  
Author(s):  
Hsin-I Wang ◽  
Yu-Chun Ho ◽  
Ya-Ping Huang ◽  
Shin-Liang Pan

Background The association between migraine and Parkinson’s disease (PD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD. Methods A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan–Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD. Results During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non-migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25–2.14, p = 0.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group ( p = 0.0041). Conclusions This study showed an increased risk of developing PD in patients with migraine.


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