Effects of amyloid precursor protein peptide APP96-110, alone or with human mesenchymal stromal cells, on recovery after spinal cord injury

Hodgetts, Stuart I.; Lovett, Sarah J.; Baron-Heeris, Danii; Fogliani, A; Sturm, M.; Heuvel, Corinna van den; Harvey, Alan R.

doi:10.4103/1673-5374.327357

Cited by 2 publications

(1 citation statement)

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“…The neuroprotective, neurotrophic and neurogenic properties of sAPPα relevant against AD and TBI are mediated via the HBS located in APP E1 domain, within residues 96–110 [ 221 ]. In addition, the peptide APP derivative APP96–110 has been shown effective towards TBI following intravenous administration [ 222 , 223 ]. In this regard, recent studies both in vitro and in vivo reported that sAPPα acute administration in mice models or its chronic delivery through gene therapy effectively ameliorated both AD and TBI symptoms, further hinting at the proposed neurotrophic and neuroprotective roles of sAPPα [ 224 , 225 ].…”

Section: Discussionmentioning

confidence: 99%

The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration

Masi

Biundo

Fiou

et al. 2023

IJMS

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Amyloid Precursor Protein (APP) and its cleavage processes have been widely investigated in the past, in particular in the context of Alzheimer’s Disease (AD). Evidence of an increased expression of APP and its amyloidogenic-related cleavage enzymes, β-secretase 1 (BACE1) and γ-secretase, at the hit axon terminals following Traumatic Brain Injury (TBI), firstly suggested a correlation between TBI and AD. Indeed, mild and severe TBI have been recognised as influential risk factors for different neurodegenerative diseases, including AD. In the present work, we describe the state of the art of APP proteolytic processing, underlining the different roles of its cleavage fragments in both physiological and pathological contexts. Considering the neuroprotective role of the soluble APP alpha (sAPPα) fragment, we hypothesised that sAPPα could modulate the expression of genes of interest for AD and TBI. Hence, we present preliminary experiments addressing sAPPα-mediated regulation of BACE1, Isthmin 2 (ISM2), Tetraspanin-3 (TSPAN3) and the Vascular Endothelial Growth Factor (VEGFA), each discussed from a biological and pharmacological point of view in AD and TBI. We finally propose a neuroprotective interaction network, in which the Receptor for Activated C Kinase 1 (RACK1) and the signalling cascade of PKCβII/nELAV/VEGF play hub roles, suggesting that vasculogenic-targeting therapies could be a feasible approach for vascular-related brain injuries typical of AD and TBI.

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