The protective effect of human platelet lysate in models of neurodegenerative disease: involvement of the Akt and MEK pathways

Abstract

Neurodegenerative diseases have huge economic and societal impacts, and place an immense emotional burden on patients and caregivers. Given that platelets have an essential physiological role in wound healing and tissue repair, human platelet lysates (HPLs) are being developed as a novel, effective biotherapy for neurodegenerative diseases. HPLs constitute abundant, readily accessible sources of physiological mixtures of many growth factors (GFs), with demonstrable effects on neuron survival and thus the development, maintenance, function and plasticity of the vertebrate nervous system. Here, we found that HPLs had marked neuroprotective abilities in cell-based models of Parkinson's disease and amyotrophic lateral sclerosis (the LUHMES and NSC-34 cell lines, respectively). The HPLs protected against specific cell death pathways (apoptosis and ferroptosis) and specific oxidative stress inducers [1-methyl-4-phenylpyridinium (MPP+) and menadione], and always afforded more protection than commonly used recombinant GFs (rGFs). The mechanism of protection of HPLs involved specific signalling pathways: whereas the Akt pathway was activated by HPLs under all conditions, the MEK pathway appeared to be more specifically involved in protection against MPP+ toxicity in LUHMES and, in a lesser extent, in staurosporine toxicity in NSC-34. Our present results suggest that HPLs-based therapies could be used to prevent neuronal loss in neurodegenerative diseases while overcoming the limitations currently associated with use of rGFs. Copyright © 2016 John Wiley & Sons, Ltd.

Past and Future of Neurotrophic Growth Factors Therapies in ALS: From Single Neurotrophic Growth Factor to Stem Cells and Human Platelet Lysates

“…We demonstrated its neuroprotective effect in in vitro and in vivo model of Parkinson's disease and its anti-inflammatory properties (102). To extend the concept to ALS, HPPL was tested on a motoneuron-like model and strongly protected from apoptosis and oxidative stress (103). Higher neuroprotection was obtained with HPPL compare to single growth factor or combination of 4 (PDGF, BDNF, BFGF, VEGF) and involved specific signaling pathway such as Akt and MEK (103).…”

“…To extend the concept to ALS, HPPL was tested on a motoneuron-like model and strongly protected from apoptosis and oxidative stress (103). Higher neuroprotection was obtained with HPPL compare to single growth factor or combination of 4 (PDGF, BDNF, BFGF, VEGF) and involved specific signaling pathway such as Akt and MEK (103). These results give a real hope for neuroprotective therapy and need to be confirmed in in vivo ALS model with ICV or IN administration of HPPL.…”

Is TNF inhibitor exposure a risk factor for amyotrophic lateral sclerosis?

“…Hence, following this hypothesis, TNFi could limit the progression of ALS . However, on the other hand, TNFα induces activation of the major survival PI3K/Akt pathway, as demonstrated in hepatocytes , and appears to be involved in motor neuron survival, as demonstrated in vivo and in vitro . TNFi may reduce the major survival pathways in motor neurons (i.e.…”

Ferroptosis in Neurological Diseases

“…Virus-inactivated and heat-treated human platelet lysate has a strong neuroprotective effect against erastin-induced ferroptosis ( Nebie et al, 2019 ) and has been developed as a novel and effective neurodegenerative therapy. Human platelet lysates can inhibit ferroptosis and reduce neuronal loss in cellular models of PD and amyotrophic lateral sclerosis (ALS) ( Gouel et al, 2017 ). Third, as another type of inhibitor, Mithramycin, DNA-binding drugs, can reduce c-Myc expression by binding to the Sp1 site in its promoter, thereby playing a role in inhibiting iron death and treating animal models of HD and AD ( Sleiman et al, 2011 ; Ratan, 2020 ).…”