ORCID Profile
0000-0002-4230-1827
Current Organisation
University of Manchester
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Publisher: Bentham Science Publishers Ltd.
Date: 05-03-2021
DOI: 10.2174/1567205018666210218163857
Abstract: Alzheimer’s disease (AD) has challenged single-target therapeutic strategies, raising the possibility that combined therapies may offer a more effective treatment strategy. There is substantial evidence for the efficacy of leptin (L) (neuroprotective hormone) and pioglitazone (P) (anti-inflammatory agent) as monotherapies in AD. We have previously shown that combination treatment of L+P in APP/PS1 mice at the onset of pathology significantly improved memory and reduced brain Aβ levels relative to control mice. In this new study, we sought to replicate our previous findings in a new cohort of APP/PS1 mice to further confirm whether the combined treatment of L+P is superior to each treatment in idually. : We have re-evaluated the effects of L+P co-treatment in APP/PS1 mice using thioflavin-S staining, MOAβ immunolabeling, and enzyme-linked immunosorbent assay (ELISA) to examine effects on Aβ levels and pathology, relative to animals that received L or P in idually. We demonstrated that a combination of L and P significantly enhances the anti-Aβ effect of L or P in the hippoc us of APP/PS1 mice. Our findings suggest that combining L and P significantly enhances the anti-Aβ effect of L or P in the hippoc us of APP/PS1 mice and maybe a potential new effective strategy for AD therapy.
Publisher: Wiley
Date: 05-12-2019
DOI: 10.1111/JNC.14909
Abstract: Axon degeneration and axonal loss is a feature of neurodegenerative disease and injury and occurs via programmed pathways that are distinct from cell death pathways. While the pathways of axonal loss following axon severing are well described, less is known about axonal loss following other neurodegenerative insults. Here we use primary mouse cortical neuron cultures grown in compartmentalized chambers to investigate the role of calcium in the degeneration of axons that occurs following a somal insult by the excitotoxin kainic acid. Calcium influx has been implicated in both excitotoxicity and axon degeneration mechanisms, however the link between a somal insult and axonal calcium increase is unclear. Live imaging of axons demonstrated that pharmacologically preventing intracellular calcium increases through the endoplasmic reticulum or mitochondria significantly (p < 0.05) reduced axon degeneration. Live calcium-imaging with the Ca
Publisher: Springer Science and Business Media LLC
Date: 15-03-2018
DOI: 10.1007/S11011-018-0203-9
Abstract: Disruption of leptin signalling has been implicated as playing a role in the development of Alzheimer's disease (AD). Leptin has previously been shown to be affected by amyloid-beta (Aβ)-related signalling however, pathways that link leptin to the disease pathogenesis have not been determined. To characterize the association between increasing age-dependent Aβ levels with leptin signalling and the vulnerable brain regions in AD, we assessed the mRNA and protein expression profile of leptin and leptin receptor (Ob-Rb) at 9 and 18-month-age in APP/PS1 mice. Immunohistochemical labelling demonstrated that leptin and Ob-Rb proteins were localised to neocortical and hippoc al neurons in APP/PS1 and wildtype (WT) mice. Neuronal leptin and Ob-Rb immunolabelling was more prominent in the neocortex of both groups at 9 month of age, while, at 18 months, labelling was reduced in the hippoc us of APP/PS1 mice relative to WT. Immunoblotting analysis demonstrated decreased hippoc al leptin levels, concomitantly with an increased Ob-Rb levels, in APP/PS1 mice compared with WT controls at 18 month of age. While no leptin mRNA was found in either of the groups analysed, Ob-Rb mRNA was significantly decreased in the hippoc us of APP/PS1 mice at both ages analysed. In addition, a significant decreased protein kinase B (Akt) activity concomitantly with an upregulation of suppressor of cytokine signaling-3 (SOCS3) and protein-tyrosine phosphatase 1B (PTP1B) transcripts was present. Thus, these results collectively indicate alterations of leptin signalling in the hippoc us of APP/PS1 mice, providing novel insights about the pathways that could link aberrant leptin signaling to the pathological changes of AD.
Publisher: Springer Science and Business Media LLC
Date: 25-04-2018
Publisher: Portland Press Ltd.
Date: 06-2021
DOI: 10.1042/NS20200101
Abstract: Cognitive dysfunction is a key symptom of ageing and neurodegenerative disorders, such as Alzheimer’s disease (AD). Strategies to enhance cognition would impact the quality of life for a significant proportion of the ageing population. The α-klotho protein may protect against cognitive decline through multiple mechanisms: such as promoting optimal synaptic function via activation of N-methyl-d-aspartate (NMDA) receptor signalling stimulating the antioxidant defence system reducing inflammation promoting autophagy and enhancing clearance of amyloid-β. However, the molecular and cellular pathways by which α-klotho mediates these neuroprotective functions have yet to be fully elucidated. Key questions remain unanswered: which form of α-klotho (transmembrane, soluble or secreted) mediates its cognitive enhancing properties what is the neuronal receptor for α-klotho and which signalling pathways are activated by α-klotho in the brain to enhance cognition how does peripherally administered α-klotho mediate neuroprotection and what is the molecular basis for the beneficial effect of the VS variant of α-klotho? In this review, we summarise the recent research on neuronal α-klotho and discuss how the neuroprotective properties of α-klotho could be exploited to tackle age- and neurodegeneration-associated cognitive dysfunction.
Publisher: Frontiers Media SA
Date: 29-11-2018
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kelsey Hanson.