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Impact of the apelin/APJ axis in the pathogenesis of Parkinson's disease with therapeutic potential

Angelopoulou E, Paudel YN, Bougea A, Piperi C

J Neurosci Res, 2021 Sep;99(9):2117-2133.
PMID: 34115895 DOI: 10.1002/jnr.24895

The pathogenesis of Parkinson's disease (PD) remains elusive. There is still no available disease-modifying strategy against PD, whose management is mainly symptomatic. A growing amount of preclinical evidence shows that a complex interplay between autophagy dysregulation, mitochondrial impairment, endoplasmic reticulum stress, oxidative stress, and excessive neuroinflammation underlies PD pathogenesis. Identifying key molecules linking these pathological cellular processes may substantially aid in our deeper understanding of PD pathophysiology and the development of novel effective therapeutic approaches. Emerging preclinical evidence indicates that apelin, an endogenous neuropeptide acting as a ligand of the orphan G protein-coupled receptor APJ, may play a key neuroprotective role in PD pathogenesis, via inhibition of apoptosis and dopaminergic neuronal loss, autophagy enhancement, antioxidant effects, endoplasmic reticulum stress suppression, as well as prevention of synaptic dysregulation in the striatum, excessive neuroinflammation, and glutamate-induced excitotoxicity. Underlying signaling pathways involve phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin, extracellular signal-regulated kinase 1/2, and inositol requiring kinase 1α/XBP1/C/EBP homologous protein. Herein, we discuss the role of apelin/APJ axis and associated molecular mechanisms on the pathogenesis of PD in vitro and in vivo and provide evidence for its challenging therapeutic potential.

Matched MeSH terms: Parkinson Disease/drug therapy*; Parkinson Disease/metabolism*
Fulltext Sleep-disordered breathing in patients with Parkinson's disease [Retracted article]

Noradina AT, Karim NA, Hamidon BB, Norlinah I, Raymond AA

Singapore Med J, 2010 Jan;51(1):60-4.
PMID: 20200778

Retraction notice: Following investigations of duplicate publication in Parkinsonism and Related Disorders 2009; 15: 670–674, we have determined that there is indeed a substantial overlap between the two articles. As such, we fully retract this paper from the published record of the Singapore Medical Journal.
Professor Teo Eng Kiong, Editor, Singapore Medical Journal
http://smj.sma.org.sg/5201/5201rec1.pdf

There are limited studies reporting the frequency of sleep-disordered breathing (SDB) in Parkinson's disease (PD), and the figures quoted are variable, ranging from 2.5 to 66 percent. This study aimed to determine the prevalence and types of SBD in PD patients attending the Universiti Kebangsaan Malaysia Medical Centre neurology clinic, and the correlation between the subjective sleep symptoms using the Parkinson's disease sleep scale (PDSS) and the objective measurements using polysomnography (PSG).
METHODS: This was a cross-sectional study involving 46 PD patients over a period of six months. The patients' demographic data, Hoehn and Yahr staging and PDSS scores were collected. The patients were then subjected to overnight PSG using the Somnomedic system.
RESULTS: There were 27 male and 19 female patients with a mean age of 64.0+/-9.7 years. 29 were Chinese, 15 Malay and 2 Indian. The mean duration of illness was 5.8+/-4.3 years. The mean PDSS score was 120.3+/-13.5. SDB was found in 54.6 percent of the patients (apnoeahypopnoea index [AHI] 5 and above), with 27.3 percent having moderate and severe SDB (AHI 15 and above). The median AHI was 6.7 (range 0-40.4). The prevalence of SDB in PD patients based on the AHI cutoffs were 27.3 percent for mild, 18.2 percent for moderate and 9.1 percent for severe. There were statistically significant positive correlations between the AHI and the neck circumference and between the AHI and the waist-hip ratio. There was no significant correlation between the AHI and PDSS, or the AHI and disease severity.
CONCLUSION: There was a high prevalence of SBD in our PD patients, which was comparable to other studies. Obstructive sleep apnoea was the dominant type of SBD. There was no correlation between the subjective sleep symptoms using the PDSS and the objective measurements using PSG.

Study site: Neurology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)

Matched MeSH terms: Parkinson Disease/complications*; Parkinson Disease/epidemiology
Fulltext LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case-control association study for Parkinson's disease

Gopalai AA, Lim JL, Li HH, Zhao Y, Lim TT, Eow GB, et al.

Mol Genet Genomic Med, 2019 Nov;7(11):e604.
PMID: 31487119 DOI: 10.1002/mgg3.604

BACKGROUND: The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K-R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population.
METHODS: Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age- and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay.
RESULTS: A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta-analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H.
CONCLUSION: This study reports that the N551K-R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.

Matched MeSH terms: Parkinson Disease/genetics*; Parkinson Disease/epidemiology
Fulltext Perception on the Quality of Life, Communication and Life Satisfaction among Individuals with Parkison's and Their Caregivers

Chu SY, Tan CL

Ethiop J Health Sci, 2019 Sep;29(5):551-558.
PMID: 31666775 DOI: 10.4314/ejhs.v29i5.4

BACKGROUND: Speech impairment, which reduces Quality of Life (QOL), frequently occurs in individuals with Parkinson's disease (PD). As speaking is required for social interaction, speech impairment can reduce one's life satisfaction. Although QOL has been well-studied in individuals with PD, the QOL of their caregivers has seldom been investigated. This study compared the QOL of individuals with PD and their caregivers. The relationships between QOL, self-rated speech scale, and life satisfaction level were examined.
METHOD: A total of 20 individuals with PD and their caregivers completed the Parkinson's disease Questionnaire-39 (PDQ-39) scale and the Life Satisfaction Scale (LSS). In addition, PD participants were asked to complete the Self-Rated Speech Scale (SRSS) to rate their speech intelligibility.
RESULT: PD participants reported significantly lower QOL scores than their caregivers. However, there was no difference between the two groups on the social support and stigma dimensions, indicating that both groups reported similar levels of social support and stigma in their daily lives. A moderate significant correlation was observed between the LSS and PDQ-39 scores in the PD group, suggesting that life satisfaction could affect their QOL. Moreover, moderate correlation was found between the LSS and SRSS, showing that participants self-reported speech intelligibility has an impact on their life satisfaction.
CONCLUSION: In general, individuals with PD showed lower QOL than their caregivers. Given that the SRSS, LSS and QOL are moderately correlated, identifying patients' perception on their speech intelligibility and life satisfaction could help clinicians to better understand their patients' needs when delivering speech therapy services.

Matched MeSH terms: Parkinson Disease/complications*; Parkinson Disease/psychology*
Fulltext MPTP-induced mouse model of Parkinson's disease: A promising direction of therapeutic strategies

Mustapha M, Mat Taib CN

Bosn J Basic Med Sci, 2021 Aug 01;21(4):422-433.
PMID: 33357211 DOI: 10.17305/bjbms.2020.5181

Among the popular animal models of Parkinson's disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). This neurotoxin exerts it neurotoxicity by causing a barrage of insults, such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert, ultimately leading to dopaminergic neuronal damage in the substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neurons of the mouse brain has led to new perspectives on PD. For decades, the MPTP-induced mouse model of PD has been the gold standard in PD research even though it does not fully recapitulate PD symptomatology, but it does have the advantages of simplicity, practicability, affordability, and fewer ethical considerations and greater clinical correlation than those of other toxin models of PD. The model has rejuvenated PD research and opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the role of MPTP in producing Parkinson-like symptoms in mice and the experimental role of the MPTP-induced mouse model. We discussed recent developments of more promising PD therapeutics to enrich our existing knowledge about this neurotoxin using this model.

Matched MeSH terms: Parkinson Disease/drug therapy*; Parkinson Disease/etiology*
Fulltext Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer's Disease

Dhakal S, Kushairi N, Phan CW, Adhikari B, Sabaratnam V, Macreadie I

Int J Mol Sci, 2019 Oct 14;20(20).
PMID: 31615073 DOI: 10.3390/ijms20205090

Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Lewy body dementia, etc. Alzheimer's Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer's Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer's Disease.

Matched MeSH terms: Parkinson Disease/diet therapy*; Parkinson Disease/metabolism
Fulltext A survey of middleware for sensor and network virtualization

Khalid Z, Fisal N, Rozaini M

Sensors (Basel), 2014;14(12):24046-97.
PMID: 25615737 DOI: 10.3390/s141224046

Wireless Sensor Network (WSN) is leading to a new paradigm of Internet of Everything (IoE). WSNs have a wide range of applications but are usually deployed in a particular application. However, the future of WSNs lies in the aggregation and allocation of resources, serving diverse applications. WSN virtualization by the middleware is an emerging concept that enables aggregation of multiple independent heterogeneous devices, networks, radios and software platforms; and enhancing application development. WSN virtualization, middleware can further be categorized into sensor virtualization and network virtualization. Middleware for WSN virtualization poses several challenges like efficient decoupling of networks, devices and software. In this paper efforts have been put forward to bring an overview of the previous and current middleware designs for WSN virtualization, the design goals, software architectures, abstracted services, testbeds and programming techniques. Furthermore, the paper also presents the proposed model, challenges and future opportunities for further research in the middleware designs for WSN virtualization.

Matched MeSH terms: Parkinson Disease
A new hybrid intelligent system for accurate detection of Parkinson's disease

Hariharan M, Polat K, Sindhu R

Comput Methods Programs Biomed, 2014 Mar;113(3):904-13.
PMID: 24485390 DOI: 10.1016/j.cmpb.2014.01.004

Elderly people are commonly affected by Parkinson's disease (PD) which is one of the most common neurodegenerative disorders due to the loss of dopamine-producing brain cells. People with PD's (PWP) may have difficulty in walking, talking or completing other simple tasks. Variety of medications is available to treat PD. Recently, researchers have found that voice signals recorded from the PWP is becoming a useful tool to differentiate them from healthy controls. Several dysphonia features, feature reduction/selection techniques and classification algorithms were proposed by researchers in the literature to detect PD. In this paper, hybrid intelligent system is proposed which includes feature pre-processing using Model-based clustering (Gaussian mixture model), feature reduction/selection using principal component analysis (PCA), linear discriminant analysis (LDA), sequential forward selection (SFS) and sequential backward selection (SBS), and classification using three supervised classifiers such as least-square support vector machine (LS-SVM), probabilistic neural network (PNN) and general regression neural network (GRNN). PD dataset was used from University of California-Irvine (UCI) machine learning database. The strength of the proposed method has been evaluated through several performance measures. The experimental results show that the combination of feature pre-processing, feature reduction/selection methods and classification gives a maximum classification accuracy of 100% for the Parkinson's dataset.

Matched MeSH terms: Parkinson Disease/classification; Parkinson Disease/diagnosis*; Parkinson Disease/physiopathology*
Brain functional connectivity patterns for emotional state classification in Parkinson's disease patients without dementia

Yuvaraj R, Murugappan M, Acharya UR, Adeli H, Ibrahim NM, Mesquita E

Behav Brain Res, 2016 Feb 1;298(Pt B):248-60.
PMID: 26515932 DOI: 10.1016/j.bbr.2015.10.036

Successful emotional communication is crucial for social interactions and social relationships. Parkinson's Disease (PD) patients have shown deficits in emotional recognition abilities although the research findings are inconclusive. This paper presents an investigation of six emotions (happiness, sadness, fear, anger, surprise, and disgust) of twenty non-demented (Mini-Mental State Examination score >24) PD patients and twenty Healthy Controls (HCs) using Electroencephalogram (EEG)-based Brain Functional Connectivity (BFC) patterns. The functional connectivity index feature in EEG signals is computed using three different methods: Correlation (COR), Coherence (COH), and Phase Synchronization Index (PSI). Further, a new functional connectivity index feature is proposed using bispectral analysis. The experimental results indicate that the BFC change is significantly different among emotional states of PD patients compared with HC. Also, the emotional connectivity pattern classified using Support Vector Machine (SVM) classifier yielded the highest accuracy for the new bispectral functional connectivity index. The PD patients showed emotional impairments as demonstrated by a poor classification performance. This finding suggests that decrease in the functional connectivity indices during emotional stimulation in PD, indicating functional disconnections between cortical areas.

Matched MeSH terms: Parkinson Disease
Fulltext Parkinson's Disease Diagnosis and Severity Assessment Using Ground Reaction Forces and Neural Networks

Veeraragavan S, Gopalai AA, Gouwanda D, Ahmad SA

Front Physiol, 2020;11:587057.
PMID: 33240106 DOI: 10.3389/fphys.2020.587057

Gait analysis plays a key role in the diagnosis of Parkinson's Disease (PD), as patients generally exhibit abnormal gait patterns compared to healthy controls. Current diagnosis and severity assessment procedures entail manual visual examinations of motor tasks, speech, and handwriting, among numerous other tests, which can vary between clinicians based on their expertise and visual observation of gait tasks. Automating gait differentiation procedure can serve as a useful tool in early diagnosis and severity assessment of PD and limits the data collection to solely walking gait. In this research, a holistic, non-intrusive method is proposed to diagnose and assess PD severity in its early and moderate stages by using only Vertical Ground Reaction Force (VGRF). From the VGRF data, gait features are extracted and selected to use as training features for the Artificial Neural Network (ANN) model to diagnose PD using cross validation. If the diagnosis is positive, another ANN model will predict their Hoehn and Yahr (H&Y) score to assess their PD severity using the same VGRF data. PD Diagnosis is achieved with a high accuracy of 97.4% using simple network architecture. Additionally, the results indicate a better performance compared to other complex machine learning models that have been researched previously. Severity Assessment is also performed on the H&Y scale with 87.1% accuracy. The results of this study show that it is plausible to use only VGRF data in diagnosing and assessing early stage Parkinson's Disease, helping patients manage the symptoms earlier and giving them a better quality of life.

Matched MeSH terms: Parkinson Disease
Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum

Haleagrahara N, Siew CJ, Mitra NK, Kumari M

Neurosci Lett, 2011 Aug 15;500(2):139-43.
PMID: 21704673 DOI: 10.1016/j.neulet.2011.06.021

An increasing large body of research on Parkinson's disease (PD) has focused on the understanding of the mechanisms behind the potential neuro protection offered by antioxidants and iron chelating agents. In this study, the protective effect of the bioflavonoid quercetin on 6-hydroxydopamine (6-OHDA)-induced model of PD was investigated. PD was induced by a single intracisternal injection of 6-hydroxydopamine (300μg) to male Sprague-Dawley rats. Quercetin treatment (30mg/kg body weight) over 14 consecutive days markedly increased the striatal dopamine and antioxidant enzyme levels compared with similar measurements in the group treated with 6-OHDA alone. There was a significant decrease in protein carbonyl content in the striatum compared with that of rats that did not receive quercetin. A significant increase in neuronal survivability was also found with quercetin treatment in rats administered 6-OHDA. In conclusion, treatment with quercetin defended against the oxidative stress in the striatum and reduced the dopaminergic neuronal loss in the rat model of PD.

Matched MeSH terms: Parkinson Disease/etiology; Parkinson Disease/metabolism*; Parkinson Disease/pathology
Fulltext Emerging pathways to neurodegeneration: Dissecting the critical molecular mechanisms in Alzheimer's disease, Parkinson's disease

Tan SH, Karri V, Tay NWR, Chang KH, Ah HY, Ng PQ, et al.

Biomed Pharmacother, 2019 Mar;111:765-777.
PMID: 30612001 DOI: 10.1016/j.biopha.2018.12.101

Neurodegenerative diseases are usually sporadic in nature and commonly influenced by a wide range of genetic, life style and environmental factors. A unifying feature of Alzheimer's disease (AD) and Parkinson's disease (PD) is the abnormal accumulation and processing of mutant or damaged intra and extracellular proteins; this leads to neuronal vulnerability and dysfunction in the brain. Through a detailed review of ubiquitin proteasome, mRNA splicing, mitochondrial dysfunction, and oxidative stress pathway interrelation on neurodegeneration can improve the understanding of the disease mechanism. The identified pathways common to AD and PD nominate promising new targets for further studies, and as well as biomarkers. These insights suggested would likely provide major stimuli for developing unified treatment approaches to combat neurodegeneration. More broadly, pathways can serve as vehicles for integrating findings from diverse studies of neurodegeneration. The evidence examined in this review provides a brief overview of the current literature on significant pathways in promoting in AD, PD. Additionally, these insights suggest that biomarkers and treatment strategies may require simultaneous targeting of multiple components.

Matched MeSH terms: Parkinson Disease/genetics; Parkinson Disease/metabolism*; Parkinson Disease/pathology
Fulltext Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside

Wang M, Ling KH, Tan JJ, Lu CB

Cells, 2020 06 18;9(6).
PMID: 32570916 DOI: 10.3390/cells9061489

Parkinson's Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Thus, regenerating functional mDA neurons in PD patients may be a cure to the disease. The proof-of-principle clinical trials showed that human fetal graft-derived mDA neurons could restore the release of dopamine neurotransmitters, could reinnervate the striatum, and could alleviate clinical symptoms in PD patients. The invention of human-induced pluripotent stem cells (hiPSCs), autologous source of neural progenitors with less ethical consideration, and risk of graft rejection can now be generated in vitro. This advancement also prompts extensive research to decipher important developmental signaling in differentiation, which is key to successful in vitro production of functional mDA neurons and the enabler of mass manufacturing of the cells required for clinical applications. In this review, we summarize the biology and signaling involved in the development of mDA neurons and the current progress and methodology in driving efficient mDA neuron differentiation from pluripotent stem cells.

Matched MeSH terms: Parkinson Disease/pathology*; Parkinson Disease/physiopathology; Parkinson Disease/therapy
Parkinson's disease and the gastrointestinal microbiome

Lubomski M, Tan AH, Lim SY, Holmes AJ, Davis RL, Sue CM

J Neurol, 2020 Sep;267(9):2507-2523.
PMID: 31041582 DOI: 10.1007/s00415-019-09320-1

Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson's disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and ageing on the GM. Roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target.

Matched MeSH terms: Parkinson Disease
Fractalkine (CX3CL1) signaling and neuroinflammation in Parkinson's disease: Potential clinical and therapeutic implications

Angelopoulou E, Paudel YN, Shaikh MF, Piperi C

Pharmacol Res, 2020 08;158:104930.
PMID: 32445958 DOI: 10.1016/j.phrs.2020.104930

Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD) with the dysregulation of microglial activity being tightly linked to dopaminergic degeneration. Fractalkine (CX3CL1), a chemokine mainly expressed by neurons, can modulate microglial activity through binding to its sole G-protein-coupled receptor (CX3CR1), expressed by microglia. Fractalkine/CX3CR1 signaling is one of the most important mediators of the communication between neurons and microglia, and its emerging role in neurodegenerative disorders including PD has been increasingly recognized. Pre-clinical evidence has revealed that fractalkine signaling axis exerts dual effects on PD-related inflammation and degeneration, which greatly depend on the isoform type (soluble or membrane-bound), animal model (mice or rats, toxin- or proteinopathy-induced), route of toxin administration, time course and specific brain region (striatum, substantia nigra). Furthermore, although existing clinical evidence is scant, it has been indicated that fractalkine may be possibly associated with PD progression, paving the way for future studies investigating its biomarker potential. In this review, we discuss recent evidence on the role of fractalkine/CX3CR1 signaling axis in PD pathogenesis, aiming to shed more light on the molecular mechanisms underlying the neuroinflammation commonly associated with the disease, as well as potential clinical and therapeutic implications.

Matched MeSH terms: Parkinson Disease/drug therapy*; Parkinson Disease/genetics; Parkinson Disease/metabolism*
Advancement in biosensor: "Telediagnosis" and "remote digital imaging"

Gopinath SCB, Ismail ZH, Shapiai MI, Yasin MNM

Biotechnol Appl Biochem, 2021 May 19.
PMID: 34009645 DOI: 10.1002/bab.2196

Current developments in sensors and actuators are heralding a new era to facilitate things to happen effortlessly and efficiently with proper communication. On the other hand, Internet of Things (IoT) has been boomed up with er potential and occupies a wide range of disciplines. This study has choreographed to design of an algorithm and a smart data-processing scheme to implement the obtained data from the sensing system to transmit to the receivers. Technically, it is called "telediagnosis" and "remote digital monitoring," a revolution in the field of medicine and artificial intelligence. For the proof of concept, an algorithmic approach has been implemented for telediagnosis with one of the degenerative diseases, that is, Parkinson's disease. Using the data acquired from an improved interdigitated electrode, sensing surface was evaluated with the attained sensitivity of 100 fM (n = 3), and the limit of detection was calculated with the linear regression value coefficient. By the designed algorithm and data processing with the assistance of IoT, further validation was performed and attested the coordination. This proven concept can be ideally used with all sensing strategies for immediate telemedicine by end-to-end communications.

Matched MeSH terms: Parkinson Disease
Fulltext Purposeless Groaning in Parkinson's Disease

Lim SY, Tan AH, Lim JL, Ahmad-Annuar A

J Mov Disord, 2018 May;11(2):87-88.
PMID: 29860787 DOI: 10.14802/jmd.18004

Purposeless groaning has been reported in advanced progressive supranuclear palsy. We present a case of purposeless groaning occurring as a primary complaint in a patient with advanced Parkinson's disease. Purposeless groaning is thought to be a manifestation of disinhibition and perseveration due to frontal-subcortical dysfunction. Proper recognition of this phenomenon will help clinicians to avoid unnecessary investigations and treatment (e.g., prescription of opioid medications).

Matched MeSH terms: Parkinson Disease
Adult Endogenous Dopaminergic Neuroregeneration Against Parkinson's Disease: Ideal Animal Models?

Vijayanathan Y, Lim SM, Tan MP, Lim FT, Majeed ABA, Ramasamy K

Neurotox Res, 2021 Apr;39(2):504-532.
PMID: 33141428 DOI: 10.1007/s12640-020-00298-7

Parkinson's disease (PD) is the second most common neurodegenerative disease. The etiology of PD remains an enigma with no available disease modifying treatment or cure. Pharmacological compensation is the only quality of life improving treatments available. Endogenous dopaminergic neuroregeneration has recently been considered a plausible therapeutic strategy for PD. However, researchers have to first decipher the complexity of adult endogenous neuroregeneration. This raises the need of animal models to understand the underlying molecular basis. Mammalian models with highly conserved genetic homology might aid researchers to identify specific molecular mechanisms. However, the scarcity of adult neuroregeneration potential in mammals obfuscates such investigations. Nowadays, non-mammalian models are gaining popularity due to their explicit ability to neuroregenerate naturally without the need of external enhancements, yet these non-mammals have a much diverse gene homology that critical molecular signals might not be conserved across species. The present review highlights the advantages and disadvantages of both mammalian and non-mammalian animal models that can be essentially used to study the potential of endogenous DpN regeneration against PD.

Matched MeSH terms: Parkinson Disease
Fulltext Suitability of Parkinson's patients for surgery in the north East coast of peninsular malaysia: a prospective analysis

Abdullah J, Abdullah MR

Malays J Med Sci, 2003 Jan;10(1):74-7.
PMID: 23365504 MyJurnal

There is no report in the English literature on the criteria for neuroablation or neuroaugmentation for the treatment of Parkinson's disease in a developing country like Malaysia. A prospective study of patients with Parkinson's disease from the north-eastern peninsular Malaysia was done to assess their suitability of surgery. Age, race, duration of illness and dementia were considered important factors towards the success of such surgical procedures. A mathematical model is suggested for future cases deemed to be suitable for neuroaugmentative or ablative surgery.

Matched MeSH terms: Parkinson Disease
Patterns of linkage disequilibrium at PARK16 may explain variances in genetic association studies

Li H, Teo YY, Tan EK

Mov Disord, 2015 Sep;30(10):1335-42.
PMID: 25758099 DOI: 10.1002/mds.26176

Reproducing genomewide association studies findings in different populations is challenging, because the reproducibility fundamentally relies on the similar patterns of linkage disequilibrium between the unknown causal variants and the genotyped single-nucleotide polymorphisms (SNPs).

Matched MeSH terms: Parkinson Disease/genetics*

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