Thiruma V Arumugam

Thiruma V Arumugam
La Trobe University · Faculty of Science, Technology and Engineering

PHD

About

238
Publications
34,997
Reads
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14,433
Citations
Introduction
A primary focus of our laboratory is to understand the cellular and molecular mechanisms and to study therapeutic targets to treat ischaemic stroke injury and Vascular Dementia (VaD).
Additional affiliations
March 2020 - present
La Trobe University
Position
  • Professor
July 2013 - March 2020
National University of Singapore
Position
  • Professor (Associate)
January 2009 - June 2013
The University of Queensland
Position
  • Senior Lecturer
Education
January 2000 - April 2004
The University of Queensland
Field of study
  • Pharmacology
January 1995 - December 1998
The University of Sydney
Field of study
  • Neuroscience

Publications

Publications (238)
Article
Full-text available
There is an increasing prevalence of Vascular Cognitive Impairment (VCI) worldwide, and several studies have suggested that Chronic Cerebral Hypoperfusion (CCH) plays a critical role in disease onset and progression. However, there is a limited understanding of the underlying pathophysiology of VCI, especially in relation to CCH. Neuroinflammation...
Article
Full-text available
Background Despite advancements in therapies, brain metastasis in patients with triple negative subtype of breast cancer remains a therapeutic challenge. Activated microglia are often observed in close proximity to, or within, malignant tumor masses, suggesting a critical role that microglia play in brain tumor progression. Annexin-A1 (ANXA1), a gl...
Article
Full-text available
Intermittent fasting (IF) remains the most effective intervention to achieve robust anti-aging effects and attenuation of age-related diseases in various species. Epigenetic modifications mediate the biological effects of several environmental factors on gene expression; however, no information is available on the effects of IF on the epigenome. He...
Article
Full-text available
Objective: Vascular dementia (VaD) is the second most common cause of dementia worldwide. The increasing contribution of lifestyle-associated risk factors to VaD has pointed towards gene-environment interactions (i.e. epigenetics). This study thus aims to investigate the DNA methylation landscape in a chronic cerebral hypoperfusion (CCH) mouse mode...
Preprint
Chronic cerebral hypoperfusion (CCH) is an important pathophysiological mechanism of vascular cognitive impairment (VCI). The heterogeneous effects of CCH complicate establishing single target therapies against VCI and its more severe form, vascular dementia (VaD). Intermittent fasting (IF) has multiple targets and is neuroprotective across a range...
Article
Full-text available
Amyloid precursor protein (APP) is an evolutionarily conserved transmembrane protein and a well-characterized precursor protein of amyloid-beta (Aβ) peptides, which accumulate in the brains of individuals with Alzheimer’s disease (AD)-related pathologies. Aβ has been extensively investigated since the amyloid hypothesis in AD was proposed. Besides...
Article
Telomeres play a critical role in maintaining cellular fate through tight regulation of cell division and DNA damage or repair. Over the years, it is established that biological ageing is defined by a gradual derangement in functionality, productivity, and robustness of biological processes. The link between telomeres and ageing is highlighted when...
Article
Full-text available
The prevalence of cerebrovascular disease increases with age, placing the elderly at a greater lifetime risk for dementia. Vascular cognitive impairment (VCI) encompasses a spectrum of cognitive deficits from mild cognitive impairment to dementia. VCI and its most severe form, vascular dementia (VaD), is becoming a major public health concern world...
Article
Full-text available
Using rigorous and clinically relevant experimental design and analysis standards, in this study, we investigated the potential of histone deacetylase (HDAC) inhibitors panobinostat and entinostat to enhance recovery of motor function after photothrombotic stroke in male mice. Panobinostat, a pan-HDAC inhibitor, is a FDA-approved drug for certain c...
Article
Chronic cerebral hypoperfusion (CCH) has been shown to be a key mechanism in vascular cognitive impairment and dementia, leading to various pathologies including blood brain barrier disruption, extracellular matrix dysfunction and inflammation. Cyclophilin A (CypA), an oxidative stress‐induced factor, is secreted into the extracellular space upon s...
Article
Background: Chronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long term cognitive impairment and memory loss. Inflammasome is an intracellular multi-protein complex that initiates an innate immune response, and is in...
Article
Background: DNA methylation landscape of a Vascular dementia (VaD) mouse model was studied to better understand the molecular happenings in the disease and hence its contribution to mixed dementia. A prophylactic intervention of intermittent fasting (IF) was introduced and its role in modulating the DNA methylation landscape was also studied. Met...
Article
Background: Chronic cerebral hypoperfusion (CCH) is an important pathophysiological mechanism in Vascular Dementia (VaD). The heterogeneous nature of CCH complicates the establishment of a stand-alone pharmacological therapy against the disease. Intermittent Fasting (IF) is neuroprotective in physiological and disease conditions, but its effects a...
Article
Full-text available
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targe...
Preprint
Multiple consensus statements have called for preclinical randomized controlled trials (pRCT) to improve translation in stroke research. Here, we investigated the efficacy of IL-17A neutralizing antibodies in a multicentric pRCT using a murine stroke model. C57/Bl.6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). Mice wer...
Article
IL-18 (interleukin-18) is elevated in hypertensive patients, but its contribution to high blood pressure and end-organ damage is unknown. We examined the role of IL-18 in the development of renal inflammation and injury in a mouse model of low-renin hypertension. Hypertension was induced in male C57BL6/J (WT) and IL-18 −/− mice by uninephrectomy, d...
Article
Full-text available
Mitochondrial dysfunction and oxidative stress are frequently observed in the early stages of Alzheimer's disease (AD). Studies have shown that presenilin-1 (PS1), the catalytic subunit of γ-secretase whose mutation is linked to familial AD (FAD), localizes to the mitochondrial membrane and regulates its homeostasis. Thus, we investigated how five...
Article
Full-text available
Chronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long-term cognitive impairment and memory loss. Here we used a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate its effect on the inna...
Article
Vascular dementia (VaD) is the second most common form of dementia and is caused by vascular pathologies resulting in chronic cerebral hypoperfusion (CCH)- induced brain injury, and ultimately cognitive impairment and memory loss. Several lines of evidence have demonstrated chronic inflammation may be involved in VaD disease progression. It is now...
Article
Aberrant Notch signalling is implicated in a number of human cancers [18, 26, 13, 21], and there is intense pharmaceutical activity being directed towards achieving clinically effective Notch pathway inhibition [7, 16].
Article
Full-text available
Vascular dementia (VaD) is a progressive cognitive impairment of vascular etiology. VaD is characterized by cerebral hypoperfusion, increased blood-brain barrier permeability and white matter lesions. An increased burden of VaD is expected in rapidly aging populations. The hippocampus is particularly susceptible to hypoperfusion, and the resulting...
Article
Chronic cerebral hypoperfusion (CCH) has been shown to initiate several inflammatory pathways that can contribute to cognitive deficits and memory loss in vascular cognitive impairment (VCI). Multi-protein complexes termed inflammasomes that may be involved in the inflammatory response to CCH has already been shown to contribute to the inflammatory...
Article
As an agonist of the classical nuclear receptors, ERα and ERβ, estrogen has been understood to inhibit the development of cardiovascular disease in pre‐menopausal women. Indeed, reduced levels of estrogen after menopause are believed to contribute to accelerated morbidity and mortality rates in women. However, estrogen replacement therapy has varia...
Article
A proper diet is important for health and longevity. Controlling the amount of food consumed is immensely beneficial as it promotes multiple cellular and molecular protective mechanisms and simultaneously prevents toxic mechanisms. Intermittent fasting (IF) is a flexible and easy-to-adopt dietary modification that helps to mitigate metabolic disord...
Preprint
Full-text available
Intermittent fasting (IF) reduces cardiovascular risk factors in animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction, but the underlying molecular mechanisms are unknown. To delineate molecular and cellular adaptations of the heart to IF, we carried out comprehensive analyses of molecular pathway...
Article
Treatments promoting post-stroke functional recovery continue to be an unmet therapeutic problem with physical rehabilitation being the most reproduced intervention in preclinical and clinical studies. Unfortunately, physiotherapy is typically effective at high intensity and early after stroke – requirements that are hardly attainable by stroke sur...
Article
Background Accumulating data suggest blood biomarkers could inform stroke etiology. Objective We investigated the performance of multiple blood biomarkers to elucidate stroke etiology with a focus on new-onset atrial fibrillation (AF) and cardioembolism. Methods Between January and December 2017, information on clinical, laboratory parameters and...
Article
Full-text available
O -GlcNAcylation ( O -linked β- N -acetylglucosaminylation) is notably decreased in Alzheimer’s disease (AD) brain. Necroptosis is activated in AD brain and is positively correlated with neuroinflammation and tau pathology. However, the links among altered O -GlcNAcylation, β-amyloid (Aβ) accumulation, and necroptosis are unclear. Here, we found th...
Preprint
Full-text available
Vascular dementia (VaD) is a progressive cognitive impairment of vascular etiology. VaD is characterized by cerebral hypoperfusion, increased blood-brain barrier permeability and white matter lesions. An increased burden of VaD is expected due to rapidly aging populations. The hippocampus is particularly susceptible to hypoperfusion, and the result...
Preprint
Full-text available
The effects of antifungal agents on the human microbiome can be challenging to study due to confounding factors such as the underlying disease states and concomitant use of antibiotics and other therapies. We elucidated longitudinal modification of gut microbiome in response to a short course (5 days) of antifungal treatment in healthy male Sprague...
Article
The CD137L-CD137 axis is a potent co-stimulatory immune checkpoint regulator that forms a bidirectional signaling pathway between the CD137 ligand (CD137L) and CD137 receptor to regulate immunological activities. This study investigated the potential involvement of the CD137L-CD137 axis on inflammasome-associated brain injury and neurological defic...
Article
Full-text available
Endothelial dysfunction, referring to a disturbance in the vascular homeostasis, has been implicated in many disease conditions including ischemic/reperfusion injury and atherosclerosis. Endothelial mitochondria have been increasingly recognized as a regulator of calcium homeostasis which has implications in the execution of diverse cellular events...
Preprint
Full-text available
Chronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long term cognitive impairment and memory loss. Here we used a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate its effect on the inna...
Article
Full-text available
Alzheimer's disease (AD) is the most common cause of dementia and the number of elderly patients suffering from AD has been steadily increasing. Despite worldwide efforts to cope with this disease, little progress has been achieved with regard to identification of effective therapeutics. Thus, active research focusing on identification of new thera...
Article
Full-text available
Background and purpose: Candida albicans is the major fungal species associated with superficial mucosal infections such as oral candidiasis as well as systemic mycoses with high morbidity and mortality. On top of the rising drug resistance, currently available antifungal agents have significant adverse effects. Nephrotoxicity is the major treatme...
Preprint
Full-text available
Intermittent fasting (IF) is a lifestyle intervention comprising a dietary regimen in which energy intake is restricted via alternating periods of fasting and ad libitum food consumption, without compromising nutritional composition. While epigenetic modifications can mediate effects of environmental factors on gene expression, no information is ye...
Article
Full-text available
Targeting the immune system and thereby modulating the inflammatory response in ischemic stroke has shown promising therapeutic potential in various preclinical trials. Among those, intravenous immunoglobulins (IVIg) have moved into the focus of attention. In a murine model of experimental stroke, we explored the therapeutic potential of IVIg on th...
Article
In this study, we investigated the potential of two histone deacetylase (HDAC) inhibitors, panobinostat and entinostat, to enhance recovery of motor function after ischemic stroke in CD-1 male mice. Panobinostat, which is a pan-HDAC inhibitor, is an FDA-approved drug for certain cancers, whereas entinostat is a class-I HDAC inhibitor and is widely...
Article
Full-text available
Diet is a significant factor in determining human well-being. Excessive eating and/or diets with higher than needed amounts of carbohydrates, salt, and fat are known to cause metabolic disorders and functional changes in the body. To compensate the ill effects, many designer diets including the Mediterranean diet, the Okinawa diet, vegetarian/vegan...
Article
Full-text available
Introduction: Intermittent fasting (IF) has been suggested to have neuroprotective effects through the activation of multiple signaling pathways. Rodents fasted intermittently exhibit enhanced hippocampal neurogenesis and long-term potentiation (LTP) at hippocampal synapses compared with sedentary animals fed an ad libitum (AL) diet. However, the...
Article
Full-text available
The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www....
Article
Ferric chloride-induced distal middle cerebral artery occlusion (MCAO) model of stroke was described in mice several years ago, however it lacked in-depth evaluation of the post-stroke functional outcomes in the animals. In this study, we reproduced the recently developed model and expanded its characterization by thorough evaluation of blood suppl...
Article
In the first part of our review, we extensively discuss the different variants of dietary restriction (DR) regimens, as well as its corresponding mechanism(s) and subsequent effects. We also provide a detailed analysis of the different epigenetic mechanisms based on current knowledge. We postulate that DR may represent an environmental intervention...
Article
Biological aging occurs concomitantly with chronological aging and is commonly burdened by the development of age-related conditions, such as neurodegenerative, cardiovascular, and a myriad of metabolic diseases. With a current global shift in disease epidemiology associated with aging and the resultant social, economic, and healthcare burdens face...
Article
The canonical Notch signalling pathway has four type I transmembrane Notch receptors (Notch1-4) and five ligands (DLL1, 2 and 3, and Jagged 1-2). Each member of this highly conserved receptor family plays a unique role in cell-fate determination during embryogenesis, differentiation, tissue patterning, proliferation and cell death [2]. As the Notch...
Article
Previous studies documented upregulation of peptidase neurolysin (Nln) after brain ischemia, however the significance of Nln function in the post‐stroke brain remained unknown. The aim of this study was to assess the functional role of Nln in the brain after ischemic stroke. Administration of a specific Nln inhibitor Agaricoglyceride A (AgaA) to mi...
Article
Full-text available
Scope: Intermittent fasting (IF) has been extensively reported to promote improved energy homeostasis and metabolic switching. While IF may be a plausible strategy to ameliorate the epidemiological burden of disease in many societies, our understanding of the underlying molecular mechanisms behind such effects is still lacking. The present study ha...
Article
Full-text available
BACE1 is the rate-limiting enzyme for amyloid-β peptides (Aβ) generation, a key event in the pathogenesis of Alzheimer’s disease (AD). By an unknown mechanism, levels of BACE1 and a BACE1 mRNA-stabilizing antisense RNA ( BACE1-AS ) are elevated in the brains of AD patients, implicating that dysregulation of BACE1 expression plays an important role...
Article
Full-text available
Post-stroke inflammation may contribute to secondary brain injury and systemic immunosuppression. Interleukin(IL)-37 is an immunosuppressive cytokine belonging to the IL-1 superfamily with no mouse homologue yet identified, the effects of which have not been studied in stroke. Here we report: (1) the effect of ischemic stroke on circulating IL-37 i...
Article
Aggregation of the microtubule-associated protein, tau, can lead to neurofibrillary tangle formation in neurons and glia which is the hallmark of tauopathy. The cellular damage induced by the formation of neurofibrillary tangles leads to neuroinflammation and consecutive neuronal death. However, detailed observation of transcriptomic changes under...
Article
The aim of this study was to assess the functional role of peptidase neurolysin (Nln) in the brain after ischemic stroke. Nln is known to inactivate bradykinin, substance P, neurotensin, and angiotensin II, which are cerebrotoxic in the ischemic brain, and to generate angiotensin-(1-7) and Met/Leu-enkephalins, which are cerebroprotective/restorativ...
Article
The aim of this study was to evaluate the potential of pharmacological modulation of adrenergic and serotoninergic systems in post-stroke motor recovery in mice. For this purpose, the effects of selective norepinephrine reuptake inhibitor atomoxetine (1 mg/kg, once a day, i.p.) and selective serotonin reuptake inhibitor fluoxetine (10 mg/kg, once a...
Article
Mitochondrial dysfunction is regarded as one of the major causes of neuronal injury in age-associated neurodegenerative diseases and stroke. Mitochondrial dysfunction leads to increased reactive oxygen species production, causing mitochondrial DNA mutations, which then results in pathological conditions. Negative conditioning of mitochondrial dysfu...
Article
Full-text available
Sirtuin 2 (SIRT2) is a family member of nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylases which appears to have detrimental roles in an array of neurological disorders such as Parkinson’s disease (PD) and Huntington’s disease (HD). In light of the recently emerging roles of sirtuins in normal physiology and pathological conditions suc...
Article
Full-text available
Stroke triggers a complex inflammatory process in which the balance between pro- and antiinflammatory mediators is critical for the development of the brain infarct. However, systemic changes may also occur in parallel with brain inflammation. Here we demonstrate that administration of recombinant IL-33, a recently described member of the IL-1 supe...
Presentation
TITLE: Comparative in vivo nephrotoxicity of a novel antifungal agent Objectives: Candida albicans is the major fungal species associated with superficial mucosal infections such as oral candidiasis as well as systemic mycoses with high morbidity and mortality. On top of the rising drug resistance, currently available antifungal agents have signifi...
Article
Full-text available
Inhibition of Notch signalling has shown anti-inflammatory properties in vivo and in vitro models of rheumatoid arthritis (RA). The objective of this study was to determine whether Notch1 might play a role in regulating T-regulatory cells (Tregs) in animal models of RA. Methods: Collagen-induced arthritis (CIA) and collagen antibody-induced arthrit...
Article
Stroke is the second leading cause of death in the world and a major cause of long-term disability. Recent evidence has provided insight into a newly described inflammatory mechanism that contributes to neuronal and glial cell death, and impaired neurological outcome following ischemic stroke - a form of sterile inflammation involving innate immune...
Article
INTRODUCTION: Chronic activation of microglia is the hallmark of numerous neuropathologies such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. The activated microglia perpetuate inflammation by releasing an array of pro-inflammatory and neurotoxic factors, which eventually exacerbate neurotoxicity and neurodegeneration upon chr...