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Cancer risk in Parkinson disease: An updated systematic review and meta-analysis

Leong YQ, Lee SWH, Ng KY

Eur J Neurol, 2021 Dec;28(12):4219-4237.
PMID: 34403556 DOI: 10.1111/ene.15069

BACKGROUND AND PURPOSE: Increasing evidence suggests significant associations between Parkinson disease (PD) and cancer risks. We conducted an updated review of studies that examined the risks of various cancer among PD patients and how this differed when cancer preceded PD diagnosis or PD diagnosis preceded cancer.
METHODS: Four databases were searched for studies that examined the association between PD and incidence of cancer from database inception to 4 June 2021. Three independent reviewers screened the articles for eligibility and extracted study data. Pooled relative risk with 95% confidence intervals were calculated using a random effects model.
RESULTS: Forty studies involving 11 case-control studies, two nested case-control studies, 22 cohort studies, and five cross-sectional studies were included. Compared to controls, PD patients had lower risks of lung, genitourinary, gastrointestinal, and haematological cancers. Conversely, higher risks of melanoma and brain cancer were noted among PD patients. No association was found between PD and risk of female cancers. Subgroup analysis found negative associations between PD patients and risks of colon cancer, rectal cancer, and non-Hodgkin lymphoma.
CONCLUSIONS: Findings from our meta-analysis suggest PD patients had lower risks of lung, genitourinary, gastrointestinal, and haematological cancers and increased risks of melanoma and brain cancer. Future research to investigate the underlying mechanisms between PD and cancers is warranted.
Fulltext Unravelling the genetic links between Parkinson's disease and lung cancer

Leong YQ, Koh RY, Chye SM, Ng KY

Biol Chem, 2023 May 25;404(6):551-567.
PMID: 36634094 DOI: 10.1515/hsz-2022-0228

Increase evidence from epidemiological studies have shown an inverse association between Parkinson's disease (PD) and lung cancer. PD and lung cancer are both geriatric diseases, where these two diseases are sharing some common genetic determinants. Several PD-associated genes including alpha synuclein (SNCA), PTEN-induced kinase 1 (PINK1), parkin, parkinsonism associated deglycase (DJ-1), leucine-rich repeat kinase 2 (LRRK2), F-box protein 7 (FBXO7) and ubiquitin C-terminal hydrolase L1 (UCHL1) were reported to have altered expressions in lung cancer patients. This indicates that certain PD-associated genes might be important in conferring anticancer effects. This review aims to depict the physiological functions of these genes, and discuss the putative roles of these PD-associated genes in lung cancer. The understanding of the roles of these genes in the lung cancer progression might be important in the identification of new treatment targets for lung cancer. Gene therapy that aims to alter the expressions of these genes could be developed for future anticancer therapy. As a result, studying the roles of these genes in lung cancer may also help to understand their involvements as well as their roles in the pathogenesis of PD.
Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death

Leong YQ, Ng KY, Chye SM, Ling APK, Koh RY

Metab Brain Dis, 2020 01;35(1):11-30.
PMID: 31811496 DOI: 10.1007/s11011-019-00516-y

Extracellular senile plaques and intracellular neurofibrillary tangles are the neuropathological findings of the Alzheimer's disease (AD). Based on the amyloid cascade hypothesis, the main component of senile plaques, the amyloid-beta (Aβ) peptide, and its derivative called amyloid precursor protein (APP) both have been found to place their central roles in AD development for years. However, the recent therapeutics have yet to reverse or halt this disease. Previous evidence demonstrates that the accumulation of Aβ peptides and APP can exert neurotoxicity and ultimately neuronal cell death. Hence, we discuss the mechanisms of excessive production of Aβ peptides and APP serving as pathophysiologic stimuli for the initiation of various cell signalling pathways including apoptosis, necrosis, necroptosis and autophagy which lead to neuronal cell death. Conversely, the activation of such pathways could also result in the abnormal generation of APP and Aβ peptides. An elucidation of actions of APP and its metabolite, Aβ, could be vital in suggesting novel therapeutic opportunities.
Fulltext Effects of Amyloid Precursor Protein Overexpression on NF-κB, Rho-GTPase and Pro-Apoptosis Bcl-2 Pathways in Neuronal Cells

Chan HH, Leong YQ, Voon SM, Pan ML, Leong CO, Lim CL, et al.

Rep Biochem Mol Biol, 2021 Jan;9(4):417-425.
PMID: 33969135 DOI: 10.52547/rbmb.9.4.417

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive dysfunction. Previous studies have suggested that amyloid plaques, mainly comprising of amyloid-beta peptides, play a pivotal role in AD pathophysiology. This study focuses on the evaluation of the effects of amyloid precursor protein (APP) overexpression on NF-κB, Rho-GTPase and Bcl-2 mediated pro-apoptotic pathways in neuronal cells.
Methods: A lentiviral transduction system was used to generate SH-SY5Y cells overexpressing APP. Immunoblotting was conducted to determine expression levels of NF-κB, Rho-GTPase, and Bcl-2 family proteins in the APP overexpressed cells.
Results: In the NF-κB signaling pathway, APP-overexpressing SH-SY5Y cells showed that there was a reduction of p-NF-κB (p< 0.05) and IKKα. Subsequently, there was upregulation of protein expression of NF-Κb, IKKβ and IκBα. On the other hand, protein expression of RhoC (p< 0.05) and Rac1/2/3 was upregulated as compared to the control group. Meanwhile, a decrease in RhoA, Cdc42 (p< 0.05) and p-Rac1/cdc42 protein levels was observed in the APP-overexpressed group. Lastly, in the pro-apoptotic pathway, the expression of Bcl-2, Bid, Bok and Puma (p< 0.05) was up regulated in the APP-overexpressed group. Downregulation of Bad and Bim expression was observed in the APP-overexpressed as compared to the control group, and Bax expression remained unchanged in the APP-overexpressed group.
Conclusion: APP overexpression regulated signaling in the NF-κB, Rho-GTPase and Bcl-2 family pathways in neuronal cells, suggesting that these are involved in promoting neuronal survival and modulating synaptic plasticity in AD. However, further studies are essential to elucidate the APP-mediated mechanism of action.
Fulltext Dengue fever and insecticide resistance in Aedes mosquitoes in Southeast Asia: a review

Gan SJ, Leong YQ, Bin Barhanuddin MFH, Wong ST, Wong SF, Mak JW, et al.

Parasit Vectors, 2021 Jun 10;14(1):315.
PMID: 34112220 DOI: 10.1186/s13071-021-04785-4

Dengue fever is the most important mosquito-borne viral disease in Southeast Asia. Insecticides remain the most effective vector control approach for Aedes mosquitoes. Four main classes of insecticides are widely used for mosquito control: organochlorines, organophosphates, pyrethroids and carbamates. Here, we review the distribution of dengue fever from 2000 to 2020 and its associated mortality in Southeast Asian countries, and we gather evidence on the trend of insecticide resistance and its distribution in these countries since 2000, summarising the mechanisms involved. The prevalence of resistance to these insecticides is increasing in Southeast Asia, and the mechanisms of resistance are reported to be associated with target site mutations, metabolic detoxification, reduced penetration of insecticides via the mosquito cuticle and behavioural changes of mosquitoes. Continuous monitoring of the status of resistance and searching for alternative control measures will be critical for minimising any unpredicted outbreaks and improving public health. This review also provides improved insights into the specific use of insecticides for effective control of mosquitoes in these dengue endemic countries.