Ryan S Anderton

University of Notre Dame Australia · Institute for Health Research

Research is increasingly focusing on gut inflammation as a contributor to Parkinson’s disease (PD). Such gut inflammation is proposed to arise from a complex interaction between various genetic, environmental and lifestyle factors, however these factors are under-characterized. This study investigated the association between PD and single-nucleotid...

Background Cognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated. Objectives This cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large...

The translocase of outer mitochondrial membrane 40 ( TOMM40 ) ‘523’ polymorphism has previously been associated with age of Alzheimer’s disease onset and cognitive functioning in non-pathological ageing, but has not been explored as a candidate risk marker for cognitive decline in Parkinson’s disease (PD). Therefore, this longitudinal study investi...

In Parkinson’s disease (PD), gut inflammation is hypothesised to contribute to α-synuclein aggregation, but gastrointestinal α-synuclein expression is poorly characterised. Cationic arginine-rich peptides (CARPs) are an emerging therapeutic option that exerts various neuroprotective effects and may target the transmission of protein aggregates. Thi...

Background The human gastrointestinal tract harbours a complex multi-kingdom community known as the microbiome. Dysbiosis refers to its disruption and is reportedly extreme in acute critical illness yet its clinical implications are unresolved. The review systematically evaluates the association between gut dysbiosis and clinical outcomes of patien...

Background Several non-motor features of Parkinson’s disease (PD) are known to adversely affect patient health-related quality of life (HRQL). However, the specific impact of neuropsychiatric complications, such as impulsive behaviour, is yet to be elucidated. Objectives The present cross-sectional, observational study aimed to investigate the eff...

[This corrects the article DOI: 10.1016/j.heliyon.2019.e02390.].

Traumatic brain injury (TBI) can be a devastating and debilitating disease to endure. Due to improvements in clinical practice, declining mortality rates have led to research into the long‐term consequences of TBI. For example, the incidence and severity of TBI have been associated with an increased susceptibility of developing neurodegenerative di...

There is considerable variability in disease progression for patients with amyotrophic lateral sclerosis (ALS) including the age of disease onset, site of disease onset, and survival time. There is growing evidence that short structural variations (SSVs) residing in frequently overlooked genomic regions can contribute to complex disease mechanisms...

Background: Gastrointestinal symptoms (GIS) in people with Parkinson's disease (PwP) are often underreported and may remain untreated. Constipation is a common nonmotor symptom that can adversely affect health-related quality of life (QoL); however, the impact of other GIS has not been adequately investigated. Objectives: To investigate the rela...

Background The human gastrointestinal tract harbours a complex multi-kingdom community known as the microb\iome. Dysbiosis refers to its disruption and is reportedly extreme in acute critical illness, yet its clinical implications are unresolved. The review systematically evaluates the relationship between gut dysbiosis and clinical outcomes of pat...

Introduction Australian Football is a dynamic team sport that requires many athletic traits to succeed. Due to this combination of traits, as well as technical skill and physicality, there are many types of injuries that could occur. Injuries are not only a hindrance to the individual player, but to the team as a whole. Many strength and conditioni...

Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleotide (TTTA) repeat variant in NEFH was selected using an in-silico short structural variant (SSV) evaluation al...

Background: The pathology underlying cognitive changes in people with Parkinson's disease (PD) is not well understood. In healthy older adults, gut microbiome composition has been associated with cognitive function. In people with PD, preliminary evidence suggests that cortical spreading of abnormal alpha-synuclein aggregates may be associated wit...

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable in...

Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleotide (TTTA) repeat variant in NEFH was selected using an in-silico SSV evaluation algorithm and investigated in...

Gut microbiome composition is associated with mood-relating behaviours, including those reflecting depression-like phenotypes. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is an effective treatment for depression, but its effects on the gut microbiome remain largely unknown. This study assessed micr...

Parkinson’s disease (PD) is an incurable, devastating disorder that is characterized by pathological protein aggregation and neurodegeneration in the substantia nigra. In recent years, growing evidence has implicated the gut environment and the gut-brain axis in the pathogenesis and progression of PD, especially in a subset of people who exhibit pr...

Background: There has been increasing recognition of the importance of the gut microbiome in Parkinson’s disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP). Methods:...

IntroductionCholesterol levels have been associated with age-related cognitive decline, however, such an association has not been comprehensively explored in people with Parkinson’s disease (PD). To address this uncertainty, the current cross-sectional study examined the cholesterol profile and cognitive performance in a cohort of PD patients.Metho...

Poly-arginine peptides R18 and R18D have previously been demonstrated to be neuroprotective in ischaemic stroke models. Here we examined the proteolytic stability and efficacy of R18 and R18D in reducing infarct core growth and preserving the ischaemic penumbra following middle cerebral artery occlusion (MCAO) in the Sprague Dawley rat. R18 (300 or...

Objective There is a critical need to establish genetic markers that explain the complex phenotypes and pathogenicity of ALS. This study identified a polymorphism in the Stathmin-2 gene and investigated its association with sporadic ALS (sALS) disease risk, age-of onset and survival duration. Methods The candidate CA repeat was systematically anal...

Abnormal 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 onse...

Genetic variants in the angiotensin-converting enzyme (ACE) (rs4343), alpha-actinin-3 (ACTN3) (rs1815739), adrenoceptor-beta-1 (ADRB1) (rs1801253), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) (rs8192678) genes have previously been associated with elite athletic performance. This study assessed the influence o...

Since the first case of the novel coronavirus emerged in late 2019 (COVID-19), it quickly spread beyond China, with reported cases in nearly all countries and territories. As these unprecedented times have resulted in significant social and economic disruption, educational institutions have been forced to implement alternative teaching and learning...

Background: While constipation is a well-known non-motor symptom which may precede the onset of the classical motor symptoms of PD, there have been few comprehensive studies of gastrointestinal (GI) symptoms in people with PD (PwP). Objectives: To investigate the spectrum of GI symptoms in an Australian PwP cohort and their relationship to use of a...

Abnormal 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 poly-T repeat is associated with age-related cognitive decline and age of onset in...

Background. Heightened impulsivity has been reported in a subset of people with Parkinson’s disease (PwP) and is considered a risk factor for the development of impulse control disorders (ICDs). However, at present, there are no recognised biochemical markers of heightened impulsivity. Objectives. To determine if ceruloplasmin, a serum marker invol...

Tertiary institutions are experiencing an increased number of enrolments, with students varying in their demographics, previous education, and academic achievement. This relative increase in undergraduate enrolments in Australia has not translated to an increase in student retention or graduate numbers. This prompts the need to explore predictors o...

Objective To test the hypothesis that rs573116164 will have disease-modifying effects in patients with superoxide dismutase 1 ( SOD1 ) familial amyotrophic lateral sclerosis (fALS), we characterized rs573116164 within a cohort of 190 patients with fALS and 560 healthy age-matched controls to assess the variant for association with various measures...

Recent studies have highlighted that a novel class of neuroprotective peptide, known as cationic arginine-rich peptides (CARPs), have intrinsic neuroprotective properties and are particularly effective anti-excitotoxic agents. As such, the present study investigated the mechanisms underlying the anti-excitotoxic properties of CARPs, using poly-argi...

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) in ischaemic stroke has been associated with neurotoxicity, blood brain barrier (BBB) disruption and intra-cerebral hemorrhage. To examine rtPA cellular toxicity we investigated the effects of rtPA on cell viability in neuronal, astrocyte and brain endothelial cell (bEnd.3) c...

Objective As structural variations may underpin susceptibility to complex neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), the objective of this study was to investigate a structural variant (SV) within sequestosome 1 ( SQSTM1 ). Methods A candidate insertion/deletion variant within intron 5 of the SQSTM1 gene was identified...

Aim: R18D is a poly-arginine peptide that has demonstrated neuroprotection in preclinical models of excitotoxicity, stroke, hypoxic-ischemic encephalopathy and traumatic brain injury. Here, we examined the peptide’s uptake in serum. Materials & methods: Healthy, male Sprague–Dawley rats were intravenously administered either 1000 nmol/kg R18D (D-en...

Background Despite extensive studies, there are still no clinically available neuroprotective treatments for traumatic brain injury. Objectives In previous studies we demonstrated beneficial treatment effects of polyarginine peptides R18 (18-mer of arginine; 300 nmol/kg) and R18D (18-mer of D-arginine; 1000 nmol/kg) in a rat model of impact-accele...

Anatomy and physiology courses are a foundation for numerous degrees, but experience some of the highest failure rates of all undergraduate health science programs (Higgins-Opitz & Tufts, 2014). While interventions have been developed in an attempt to remediate this concerning phenomenon, there is a paucity of evidence to determine the reason anato...

The underlying genetic and molecular mechanisms that drive amyotrophic lateral sclerosis (ALS) remain poorly understood. Structural variants within the genome can play a significant role in neurodegenerative disease risk, such as the repeat expansion in C9orf72 and the tri-nucleotide repeat in ATXN2, both of which are associated with familial and s...

Although typically framed as a motor disorder, people with Parkinson’s disease (PD) may experience a plethora of other non-motor symptoms that may be equally debilitating. The management of cognitive impairment is an area of growing clinical interest given its heterogeneous manifestations and the increased relative risk of dementia, hence there is...

We have previously demonstrated that Cationic Arginine-Rich Peptides (CARPs) and in particular poly-arginine-18 (R18; 18-mer of arginine) exhibit potent neuroprotective properties in both in vitro and in vivo neuronal injury models. Based on the current literature, there is a consensus that arginine residues by virtue of their positive charge and g...

We have previously demonstrated that the poly-arginine peptide R18 can improve histological and functional outcomes following traumatic brain injury (TBI) in the Sprague–Dawley rat. Since D-enantiomer peptides are often exploited in pharmacology for their increased stability and potency, the present study compared the effects of R18 and its D-enant...

Poly-arginine peptide-18 (R18) has recently emerged as a highly effective neuroprotective agent in experimental stroke models, and is particularly efficacious in protecting cortical neurons against glutamic acid excitotoxicity. While we have previously demonstrated that R18 can reduce excitotoxicity-induced neuronal calcium influx, other molecular...

Poly-arginine peptide-18 (R18) is neuroprotective in different rodent middle cerebral artery occlusion (MCAO) stroke models. In this study, we examined whether R18 treatment could reduce ischemic brain injury and improve functional outcome in a nonhuman primate (NHP) stroke model. A stroke was induced in male cynomolgus macaques by MCAO distal to t...

Genetic variants in the angiotensin-converting enzyme (ACE) and alpha actinin-3 (ACTN3) genes have been associated with elite sport athletic performance. The present study aimed to investigate the frequency of each polymorphism in a cohort of elite Australian Football (AF) athletes. To achieve this, 47 players from an Australian Football League (AF...

Introduction: Patients with Parkinson's disease (PD) commonly experience cognitive deficits and some also develop impulse control disorders (ICDs); however, the relationship between impulsivity and cognitive dysfunction remains unclear. This study investigated whether trait impulsivity associates with mild cognitive impairment (MCI), or is altered...

Despite being recognised primarily as a motor disorder, gastrointestinal (GI) dysfunction is one of the first symptoms reported by individuals with Parkinson’s disease (PD). This is believed to be due to a shift in microbiota composition towards an unbalanced, dysbiotic nature, with increased intestinal inflammation. Furthermore, characteristic Lew...

Glioblastoma (GBM) are lethal primary brain tumours whose pathogenesis is aided, at least partly, via a pro-tumorigenic microenvironment. This study investigated whether microglia, a cell component of the GBM microenvironment, mediates pro-tumorigenic properties via the action of cyclophilin A (CypA), a potent secretable chemokine and cytoprotectan...

The interaction between the gut microbiota and alpha-synuclein (αSyn) aggregation in Parkinson’s disease (PD) is receiving increasing attention. The objective of this study was to investigate gut microbiota, and effects of an inflammatory lipopolysaccharide (LPS) trigger in a human αSyn over-expressing mouse model of PD (Thy1-αSyn). Stool samples f...

Background: Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson’s disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. Methods: Serum homocysteine, folate and vitamin B12 levels we...

Parkinson’s disease (PD) is a common neurodegenerative disorder which affects approximately 10 million people worldwide. This debilitating neurological disorder is a progressive disease, primarily diagnosed and characterized by the onset of four cardinal motor symptoms; tremor, rigidity, bradykinesia and postural instability. However, PD also has a...

We examined the neuroprotective efficacy of the poly-arginine peptide R18 and its D-enantiomer R18D in a perinatal hypoxic-ischaemic (HI) model in P7 Sprague-Dawley rats. R18 and R18D peptides were administered intraperitoneally at doses of 30, 100, 300 or 1000 nmol/kg immediately after HI (8% O2/92%N2 for 2.5 h). The previously characterised neuro...

The current study aimed to determine whether previously identified candidate polymorphisms were associated with match performance in sub-elite Australian Rules Football (ARF) players. The genotypes of thirty players were analysed along with 3x1-kilometre time trial results, ARF-specific skill assessments (handball and kicking), and match performanc...

In elite sporting codes, the identification and promotion of future athletes into specialised talent pathways is heavily reliant upon objective physical, technical, and tactical characteristics, in addition to subjective coach assessments. Despite the availability of a plethora of assessments, the dependence on subjective forms of identification re...

Hypoxic‐ischaemic encephalopathy (HIE) remains the leading cause of mortality and morbidity in neonates, with no available neuroprotective therapeutic agent. In the development of a therapeutic for HIE, we examined the neuroprotective efficacy of the poly‐arginine peptide R18D (arginine 18 mer synthesised with D‐arginine) in a perinatal model of hy...

Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is onl...

Background: Impulsive behaviour has become increasingly recognised as a neuropsychiatric complication of Parkinson’s disease (PD). Thought to be a product of compromised cognitive control, the spectrum of impulsive behaviours in PD ranges from cognitive disinhibition to impulse control disorders (ICDs). Objective: At present, there are no indicator...

We have previously demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties, with poly-arginine peptide R18 identified as being highly effective at reducing infarct volume following middle cerebral artery occlusion (MCAO) in the Sprague Dawley rat. Since peptides synthesised using D-isoform amino acids ha...

Photomicrographs of histological sections of kidney and liver tissue. Representative H & E stained 10 μm sections obtained from vehicle (saline), R18 or R18D (300 nmol/kg) treated animals approximately 24 hours after treatment administration. Magnification X400. (PPT)

Weight loss at 24-hours after permanent MCAO. Treatment groups are vehicle (saline), R18 and R18D (300 nmol/kg). Values are mean ± SD; n = 8–10. Note: an animal that died several hours before the 24-hour post-MCAO study end-point was not included. (PPT)

Traumatic brain injury (TBI) has a devastating effect on victims and their families, and has profound negative societal and economic impacts, a situation that is further compounded by the lack of effective treatments to minimise injury after TBI. The current strategy for managing TBI is partly through preventative measures and partly through surgic...

Cationic arginine-rich and poly-arginine peptides (referred to as CARPs) have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI) shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1...