Warren P Tate

Warren P Tate
University of Otago · Centre for Brain Health Research

About

250
Publications
20,757
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
9,129
Citations

Publications

Publications (250)
Article
Full-text available
Soluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer’s disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse mo...
Article
Full-text available
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease now well-documented as having arisen commonly from a viral infection, but also from other external stressors, like exposure to agricultural chemicals, other types of infection, surgery, or other severe stress events. Research has shown these events produce a systemic molecular...
Article
Full-text available
Secreted amyloid precursor protein alpha (sAPPα) processed from a parent human brain protein, APP, can modulate learning and memory. It has potential for development as a therapy preventing, delaying, or even reversing Alzheimer’s disease. In this study a comprehensive analysis to understand how it affects the transcriptome and proteome of the huma...
Article
Full-text available
Alzheimer’s disease (AD) is a neurodegenerative disorder with an increasing need for developing disease-modifying treatments as current therapies only provide marginal symptomatic relief. Recent evidence suggests the γ-aminobutyric acid (GABA) neurotransmitter system undergoes remodeling in AD, disrupting the excitatory/inhibitory (E/I) balance in...
Preprint
Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease with variable severity throughout the ongoing illness. Patients experience relapses where symptoms increase in severity, leaving them with a marked reduction in quality of life. Previous work has investigated molecular differences between ME/CFS patients and...
Article
Full-text available
Introduction: Early intervention in Alzheimer's disease (AD) requires the development of an easily administered test that is able to identify those at risk. Focusing on microRNA robustly detected in plasma and standardizing the analysis strategy, we sought to identify disease-stage specific biomarkers. Methods: Using TaqMan microfluidics arrays...
Article
The Maillard reaction, a spontaneous 'one pot' reaction between amino acids and reducing sugars that occurs at low reactant concentrations and low temperatures, is a good candidate for having played a role in the origin of life on the Earth. In view of the probability that RNA and DNA were preceded by an evolutionary forerunner with a more straight...
Preprint
Full-text available
Soluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer’s disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse mo...
Article
Full-text available
Regulation of AMPA receptor expression by neuronal activity and neuromodulators is critical to the expression of both long-term potentiation (LTP) and memory. In particular, Ca ²⁺ -permeable AMPARs (CP-AMPAR) play a unique role in these processes due to their transient, activity-regulated expression at synapses. Secreted amyloid precursor protein-a...
Article
Background: Secreted amyloid precursor protein-alpha (sAPPα) can enhance memory and is neurotrophic and neuroprotective across a range of disease-associated insults, including amyloid-β toxicity. In a significant step toward validating sAPPα as a therapeutic for Alzheimer's disease (AD), we demonstrated that long-term overexpression of human sAPPα...
Article
Early intervention in Alzheimer’s disease (AD) requires development of an easily administered test able to identify those at risk. Focusing on microRNA robustly detected in plasma and standardizing the analysis, we sought to identify disease‐stage specific biomarkers. Using TaqMan microfluidics arrays and a statistical consensus approach, we assess...
Article
Full-text available
Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a lifelong debilitating disease with a complex pathology not yet clearly defined. Susceptibility to ME/CFS involves genetic predisposition and exposure to environmental factors, suggesting an epigenetic association. Epigenetic studies with other ME/CFS cohorts have used array...
Article
Full-text available
A significant number of SARS-CoV-2 (COVID-19) pandemic patients have developed chronic symptoms lasting weeks or months which are very similar to those described for myalgic encephalomyelitis/chronic fatigue syndrome. This paper reviews the current literature and understanding of the role that mitochondria, oxidative stress and antioxidants may pla...
Article
Full-text available
Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious and complex physical illness that affects all body systems with a multiplicity of symptoms, but key hallmarks of the disease are pervasive fatigue and 'post-exertional malaise', exacerbation after physical and/or mental activity of the intrinsic fatigue and other...
Article
Full-text available
Alzheimer’s disease (AD), the most common chronic neurodegenerative disorder, has complex neuropathology. The principal neuropathological hallmarks of the disease are the deposition of extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles with neuroinflammation, a compromised blood-brain barrier (BBB) integrity, and neuronal synaptic dys...
Preprint
Full-text available
Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious and complex physical illness that affects all body systems with a multiplicity of symptoms, but key hallmarks of the disease are pervasive fatigue and ‘post-exertional malaise’, exacerbation after physical and/or mental activity of the intrinsic fatigue and other s...
Article
Alzheimer's disease (AD) is the leading type of dementia worldwide. With an increasing burden of an aging population coupled with the lack of any foreseeable cure, AD warrants the current intense research effort on the toxic effects of an increased concentration of beta‐amyloid (Aβ) in the brain. Glutamate is the main excitatory brain neurotransmit...
Article
Full-text available
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no cognition-restoring therapies exist. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Increasing evidence suggests a remodeling of the GABAergic system in AD, which might represent an important therapeutic target. An inverse agon...
Article
Full-text available
Secreted amyloid precursor protein-alpha (sAPP␣) has growth factor-like properties and can modulate long-term potentiation (LTP) and memory. Here, we demonstrate that exposure to sAPP␣ converts short-lasting LTP into protein-synthesis-dependent late LTP in hippocampal slices from male rats. sAPP␤ had no discernable effect. We hypothesized that sAPP...
Article
Full-text available
Alzheimer's disease (AD) is a complex and chronic neurodegenerative disorder that involves a progressive and severe decline in cognition and memory. During the last few decades a considerable amount of research has been done in order to better understand tau-pathology, inflammatory activity and neuronal synapse loss in AD, all of them contributing...
Article
Full-text available
Alzheimer’s Disease (AD) is the leading type of dementia worldwide. Despite an increasing burden of disease due to a rapidly ageing population, there is still a lack of complete understanding of the precise pathological mechanisms which drive its progression. Glutamate is the main excitatory neurotransmitter in the brain and plays an essential role...
Article
Full-text available
Secreted amyloid precursor protein-alpha (sAPPα), generated by enzymatic processing of the APP, possesses a range of neurotrophic and neuroprotective properties and plays a critical role in the molecular mechanisms of memory and learning. One of the key active regions of sAPPα is the central APP domain (E2) that contains within it the tripeptide se...
Article
Full-text available
Secreted amyloid precursor protein-α (sAPPα) is a neuroprotective and memory-enhancing molecule, however, the mechanisms through which sAPPα promotes these effects are not well understood. Recently, we have shown that sAPPα enhances cell-surface expression of glutamate receptors. Activity-related cytoskeletal-associated protein Arc (Arg3.1) is an i...
Article
Full-text available
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe fatigue illness that occurs most commonly following a viral infection, but other physiological triggers are also implicated. It has a profound long-term impact on the life of the affected person. ME/CFS is diagnosed primarily by the exclusion of other fatigue illnesses, but the...
Article
Processing of the amyloid precursor protein by alternative secretases results in ectodomain shedding of either secreted amyloid precursor protein-α (sAPPα) or its counterpart secreted amyloid precursor protein-β (sAPPβ). Although sAPPα contains only 16 additional amino acids at its C-terminus compared to sAPPβ, it displays significantly greater pot...
Article
Full-text available
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood disease affecting 0.2%–2% of the global population. To gain insight into the pathophysiology of ME/CFS in New Zealand, we examined the transcriptomes of peripheral blood mononuclear cells by RNA-seq analysis in a small well-characterized patient group (10 patients),...
Data
Supplementary_Material – Supplemental material for Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome
Data
Supplementary_references_used_to_support_statements_in_the_text – Supplemental material for Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome
Article
Full-text available
Alzheimer's disease (AD) is a neurodegenerative disease driven in large part by accumulated deposits in the brain of the amyloid precursor protein (APP) cleavage product amyloid-β peptide (Aβ). However, AD is also characterised by reductions in secreted amyloid precursor protein-alpha (sAPPα), an alternative cleavage product of APP. In contrast to...
Article
Full-text available
Translational stop codons, UAA, UAG, and UGA, form an integral part of the universal genetic code. They are of significant interest today for their underlying fundamental role in terminating protein synthesis, but also for their potential utilisation for programmed alternative translation events. In diverse organisms, UAA has wide usage, but it is...
Article
Full-text available
A neuroinflammatory paradigm is presented to help explain the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The hypothalamic paraventricular nucleus (PVN) is responsible for absorbing and processing multiple, incoming and convergent ‘stress’ signals, and if this cluster of neurons were affected (by neuroinflammatio...
Article
When a stop codon is at the 80S ribosomal A site, there are six nucleotides (+4 to +9) downstream that are inferred to be occupying the mRNA channel. We examined the influence of these downstream nucleotides on translation termination success or failure in mammalian cells at the three stop codons. The expected hierarchy in the intrinsic fidelity of...
Article
Secreted amyloid precursor protein-α (sAPPα) is a neurotrophic and neuroprotective molecule which can enhance learning and synaptic plasticity. Aging is associated with memory decline and impaired long-term potentiation (LTP). SAPPα therefore has potential as a nootropic agent which could be used to offset age-related cognitive decline. In this stu...
Article
Full-text available
In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ1–42) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administrati...
Article
Full-text available
It was Francis Crick who first asked why the ribosome contains so much RNA, and discussed the implications of this for the flow of genetic information from DNA to protein. Remarkable advances in our understanding of the ribosome and protein synthesis, including the recent publication of two mammalian mitochondrial ribosome structures, have shed new...
Article
Full-text available
Frameshifting during translation of viral or in rare cases cellular mRNA results in the synthesis of proteins from two overlapping reading frames within the same mRNA. In HIV-1 the protease, reverse transcriptase, and integrase enzymes are in a second reading frame relative to the structural group-specific antigen (gag), and their synthesis is depe...
Article
Full-text available
HIV-1 utilises -1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating -1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the 'intercodon')...
Article
Symbiosis islands are integrative and conjugative mobile genetic elements that convert nonsymbiotic rhizobia into nitrogen-fixing symbionts of leguminous plants. Excision of the Mesorhizobium loti symbiosis island ICEMlSym(R7A) is indirectly activated by quorum sensing through TraR-dependent activation of the excisionase gene rdfS. Here we show tha...
Article
Full-text available
Background Differential processing of the amyloid precursor protein liberates either amyloid-ß, a causative agent of Alzheimer’s disease, or secreted amyloid precursor protein-alpha (sAPPα), which promotes neuroprotection, neurotrophism, neurogenesis and synaptic plasticity. The underlying molecular mechanisms recruited by sAPPα that underpin these...
Article
Anti-Müllerian hormone (AMH) has both paracrine and hormonal actions that occur at different AMH concentrations, and in cells with different densities of its specific receptor (Amhr2). This diversity is not explained by canonical AMH signaling. We report that Amhr2 has two splice variants: Amhr2Δ2 (AMH binding site) and Amhr2Δ9/10 (kinase domain)....
Article
Full-text available
Dimers of tRNAs can form through quasi self-complementary anticodon-anticodon interactions, for example at neutral pH in yeast tRNA Asp(GUC) and at pH 4.5 in Escherichia coli tRNA Gly(GCC) through a partially protonated interaction. The requirements for tRNA oligomerization, and the factors that prevented higher orders of structures forming were ex...
Article
Full-text available
Long-term potentiation (LTP) is widely accepted as a cellular mechanism underlying memory processes. It is well established that LTP persistence is strongly dependent on activation of constitutive and inducible transcription factors, but there is limited information regarding the downstream gene networks and controlling elements that coalesce to st...
Data
Functional Annotation Clustering (DAVID Analysis) of LRGs at 5 h. Genes with annotations related to calcium and calmodulin. Enrichment score 1.42. Associations between the 5 h LRG sets and their annotations are illustrated above. The region in grey illustrates the common annotation across the cluster with areas in black illustrating the differences...
Data
Functional Annotation Clustering (DAVID Analysis) of LRGs at 5 h. Genes with annotations related to ion channels. Enrichment score 1.59. Associations between the 5 h LRG sets and their annotations are illustrated above. The region in grey illustrates the common annotation across the cluster with areas in black illustrating the differences in annota...
Data
Functional Annotation Clustering (DAVID Analysis) of LRGs at 5 h. Genes with annotations related to the synapse. Enrichment score 1.37. Associations between the 5 h LRG sets and their annotations are illustrated above. The region in grey illustrates the common annotation across the cluster with areas in black illustrating the differences in annotat...
Data
Functional Annotation Clustering (DAVID Analysis) of LRGs at 24 h. Genes with annotations related to protein kinases, Enrichment score 1.98. Associations between the 24 h LRG sets and their annotations are illustrated above. The region in grey illustrates the common annotation across the cluster with areas in black illustrating the differences in a...
Data
Annotated genes associated with 24 h IPA Biological Function Protein Synthesis. (XLSX)
Data
Annotated genes associated with 5 h IPA Canonical Pathways. (XLSX)
Data
Annotated genes differentially expressed at 5 h post-tetanization ranked by p-value. (XLS)
Data
Annotated genes differentially expressed at 24 h post-tetanization ranked by p-value. (XLSX)
Data
List of primers used for real-time qPCR. (DOC)
Data
Functional Annotation Clustering (DAVID Analysis) of LRGs at 24 h. Genes with annotations related to phosphorylation. Enrichment score 2.58. Associations between the 24 h LRG sets and their annotations are illustrated above. The region in grey illustrates the common annotation across the cluster with areas in black illustrating the differences in a...
Data
Expression of significant LRG genes across time. (DOC)
Data
Targets of miR-24-1 predicted by TargetScan, miRanda and PicTar. (XLSX)
Data
Targets of miR-34a predicted by TargetScan, miRanda and PicTar. (XLSX)
Data
Genes with sequence motifs from 5 h LRG list corresponding to rno-MIR330-3p. (XLSX)
Article
Amyloid precursor protein (APP) is an integral membrane glycoprotein present at high levels in nerve cells. Two soluble secreted forms, sAPPα and sAPPβ, are processed from APP by two mutually exclusive proteolytic pathways. sAPPα shows a range of neuroprotective and growth factor properties, including reduction of neuronal injury and improvement in...
Poster
Full-text available
MicroRNA are small non-coding RNA approximately 22 nucleotides in length that regulate gene expression. Recently, low levels of microRNA have been identified in the circulatory system. Within plasma they have been localized within high density lipoproteins (HDL), exosomes, free flowing either independently of any type of vesicle compartment, or f...
Article
Full-text available
The RNA world concept has wide, though certainly not unanimous, support within the origin-of-life scientific community. One view is that life may have emerged as early as the Hadean Eon 4.3-3.8 billion years ago with an atmosphere of high CO(2) producing an acidic ocean of the order of pH 3.5-6. Compatible with this scenario is the intriguing propo...
Article
The canonical view of the maintenance of long-term potentiation (LTP), a widely accepted experimental model for memory processes, is that new gene transcription contributes to its consolidation; however, the gene networks involved are unknown. To address this issue, we have used high-density Rat 230.2 Affymetrix arrays to establish a set of genes i...
Article
Full-text available
Inherited immunodeficiency disorders can be caused by mutations in any one of a large number of genes involved in the function of immune cells. Here, we describe two families with an autosomal recessive inherited immunodeficiency disorder characterized by increased susceptibility to infection and autoimmunity. Genetic linkage studies mapped the dis...