Richard Killick
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View article: Transcriptomic analysis of plasma small extracellular vesicles identifies potential diagnostic biomarkers for Parkinson's disease dementia
Transcriptomic analysis of plasma small extracellular vesicles identifies potential diagnostic biomarkers for Parkinson's disease dementia Open
View article: Drug repurposing for Alzheimer’s disease: a Delphi consensus and stakeholder consultation
Drug repurposing for Alzheimer’s disease: a Delphi consensus and stakeholder consultation Open
View article: Transcription-Driven Repurposing of Cardiotonic Steroids for Lithium Treatment of Severe Depression
Transcription-Driven Repurposing of Cardiotonic Steroids for Lithium Treatment of Severe Depression Open
Lithium is prescribed as a mood stabilizer for bipolar disorder and severe depression. However, the mechanism of action of lithium is unknown and there are major side effects associated with prolonged medication. This motivates a search fo…
View article: Blocking the Dkk1-LRP6 interaction prevents acute amyloid-β-driven cognitive impairment
Blocking the Dkk1-LRP6 interaction prevents acute amyloid-β-driven cognitive impairment Open
View article: Transcription driven repurposing of cardiotonic steroids for Lithium treatment of severe depression
Transcription driven repurposing of cardiotonic steroids for Lithium treatment of severe depression Open
Lithium is prescribed as a mood stabiliser in bipolar disorder and severe depression. However, the mechanism of action of Lithium is unknown and there are major side effects associated with prolonged medication. This motivates a search for…
View article: ROCK inhibitors alter brain proteomic profiles and tau phosphorylation in iPSC‐derived human neurons and mouse model of Alzheimer’s disease
ROCK inhibitors alter brain proteomic profiles and tau phosphorylation in iPSC‐derived human neurons and mouse model of Alzheimer’s disease Open
Background We aim to investigate efficacies of Ras homolog (Rho)‐associated kinases (ROCK) inhibitors on Alzheimer’s disease (AD) pathological proteins in human induced pluripotent stem cell (iPSC)‐differentiated human neurons and the P301…
View article: WNT7A-positive dendritic cytonemes control synaptogenesis in cortical neurons
WNT7A-positive dendritic cytonemes control synaptogenesis in cortical neurons Open
Synaptogenesis involves the transformation of dendritic filopodial contacts into stable connections with the exact apposition of synaptic components. Signalling triggered by Wnt/β-catenin and calcium has been postulated to aid this process…
View article: Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis
Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis Open
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to pr…
View article: Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease
Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease Open
Introduction The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line P…
View article: Masking the transmembrane region of the amyloid β precursor protein as a safe means to lower amyloid β production
Masking the transmembrane region of the amyloid β precursor protein as a safe means to lower amyloid β production Open
Introduction Reducing brain levels of both soluble and insoluble forms of amyloid beta (Aβ) remains the primary goal of most therapies that target Alzheimer's disease (AD). However, no treatment has so far resulted in patient benefit, and …
View article: Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer’s Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil
Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer’s Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil Open
The pan Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor fasudil acts as a vasodilator and has been used as a medication for post-cerebral stroke for the past 29 years in Japan and China. More recently, based on the in…
View article: Wnt-7a-positive dendritic cytonemes induce synaptogenesis in cortical neurons
Wnt-7a-positive dendritic cytonemes induce synaptogenesis in cortical neurons Open
Summary Neuronal circuits evolve as a precisely patterned network. In this context, a growing neuron must locate the appropriate target area on a neurite of a neighbouring cell with which to connect. Controlled target selection involves de…
View article: NRF2: An emerging role in neural stem cell regulation and neurogenesis
NRF2: An emerging role in neural stem cell regulation and neurogenesis Open
View article: Neurodegenerative disease associated pathways in brain of the triple transgenic Alzheimer’s model are reversed in vivo following two weeks peripheral administration of fasudil
Neurodegenerative disease associated pathways in brain of the triple transgenic Alzheimer’s model are reversed in vivo following two weeks peripheral administration of fasudil Open
The pan ROCK inhibitor fasudil acts as a vasodilator and has been used as a medication post cerebral stroke for the past 27 years in Japan and China. More recently, on the basis of the involvement of ROCK inhibition on synaptic function, n…
View article: In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer’s disease
In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer’s disease Open
View article: <i>In vivo</i>multi-parametric manganese-enhanced MRI for detecting senile plaques in rodent models of Alzheimer’s disease
<i>In vivo</i>multi-parametric manganese-enhanced MRI for detecting senile plaques in rodent models of Alzheimer’s disease Open
Senile plaques are a hallmark of Alzheimer’s disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remai…
View article: Transcription-based drug repurposing for COVID-19
Transcription-based drug repurposing for COVID-19 Open
View article: Dickkopf-1 Overexpression <i>in vitro</i> Nominates Candidate Blood Biomarkers Relating to Alzheimer’s Disease Pathology
Dickkopf-1 Overexpression <i>in vitro</i> Nominates Candidate Blood Biomarkers Relating to Alzheimer’s Disease Pathology Open
Background: Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer’s disease (AD). However, the effect of DKK1 expression on protein expression, and whet…
View article: Using the SARS Infection Transcriptional Signature to Identify Potential Treatments for Covid-19
Using the SARS Infection Transcriptional Signature to Identify Potential Treatments for Covid-19 Open
Gene expression data associated with viral infection of human cell lines is harnessed to define a conserved viral response signature. Drugs that tend to drive gene expression in the direction of the cellular viral response are significantl…
View article: Using the SARS Infection Transcriptional Signature to Identify Potential Treatments for Covid-19
Using the SARS Infection Transcriptional Signature to Identify Potential Treatments for Covid-19 Open
Gene expression data associated with viral infection of human cell lines is harnessed to define a conserved viral response signature. Drugs that tend to drive gene expression in the direction of the cellular viral response are significantl…
View article: Correction to: Wnt3a induces exosome secretion from primary cultured rat microglia
Correction to: Wnt3a induces exosome secretion from primary cultured rat microglia Open
View article: Bridging integrator 1 protein loss in Alzheimer’s disease promotes synaptic tau accumulation and disrupts tau release
Bridging integrator 1 protein loss in Alzheimer’s disease promotes synaptic tau accumulation and disrupts tau release Open
Polymorphisms associated with BIN1 (bridging integrator 1) confer the second greatest risk for developing late-onset Alzheimer’s disease. The biological consequences of this genetic variation are not fully understood; however, BIN1 is a bi…
View article: P3‐245: DKK1 OVEREXPRESSION IN VITRO NOMINATES PROTEINS PREDICTING ALZHEIMER'S PATHOLOGY IN BLOOD
P3‐245: DKK1 OVEREXPRESSION IN VITRO NOMINATES PROTEINS PREDICTING ALZHEIMER'S PATHOLOGY IN BLOOD Open
Multiple lines of evidence suggest that Wnt signalling mediates amyloid β (Aβ) induced neurotoxicty and DKK1, a regulator of Wnt signalling, is induced by Aβ. Silencing DKK1 prevented Aβ induced phenotypes and protects synapses from the to…
View article: Loss of the Alzheimer’s-linked bridging integrator 1 (BIN1) protein affects synaptic structure and disrupts tau localisation and release
Loss of the Alzheimer’s-linked bridging integrator 1 (BIN1) protein affects synaptic structure and disrupts tau localisation and release Open
Background Post-translational modifications of tau modify its interaction with binding partners and cause tau mislocalisation and altered tau function in Alzheimer’s disease (AD). The AD risk gene BIN1, is a binding partner for tau, howeve…
View article: Identifying Novel Candidates for Re-Purposing as Potential Therapeutic Agents for Alzheimer’s disease
Identifying Novel Candidates for Re-Purposing as Potential Therapeutic Agents for Alzheimer’s disease Open
The current paper describes the identification of novel candidate compounds for repositioning as treatments for Alzheimer’s disease (AD) from the CMAP library. Candidate compounds were identified based on inverse correlation with transcrip…
View article: A role for APP in Wnt signalling links synapse loss with β-amyloid production
A role for APP in Wnt signalling links synapse loss with β-amyloid production Open
View article: Clusterin Is Required for β-Amyloid Toxicity in Human iPSC-Derived Neurons
Clusterin Is Required for β-Amyloid Toxicity in Human iPSC-Derived Neurons Open
Our understanding of the molecular processes underlying Alzheimer's disease (AD) is still limited, hindering the development of effective treatments, and highlighting the need for human-specific models. Advances in identifying components o…
View article: Amyloid β synaptotoxicity is Wnt‐PCP dependent and blocked by fasudil
Amyloid β synaptotoxicity is Wnt‐PCP dependent and blocked by fasudil Open
Introduction Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are tox…
View article: FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system
FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system Open
Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence …
View article: [P4–130]: β‐AMYLOID SYNAPTOTOXICITY DRIVES β‐AMYLOID PRODUCTION
[P4–130]: β‐AMYLOID SYNAPTOTOXICITY DRIVES β‐AMYLOID PRODUCTION Open
Increased levels of Aβ destroy the connections between the nerve cells. This synaptotoxic property of Aβ is likely the main driver of Alzheimer's disease. Our contention is that this key effect is driven by dysregulation of Wnt signaling, …