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Nanomaterials successfully cross the BBB for neuroregeneration

Neurodegenerative disorders are associated with high socioeconomic costs and, for countries with a rapidly ageing population, this is a matter of grave concern. EU researchers investigated the use of nanomaterials to find solutions.
Nanomaterials successfully cross the BBB for neuroregeneration
Insufficient knowledge of underlying neurological mechanisms in health and disease has so far resulted in poor bench-to-bedside translation of neuroprotective strategies. This is exacerbated by the inability to efficiently deliver neuroprotectant drugs to the brain as crossing the blood–brain barrier (BBB) is an issue.

Nanoneuroscience could revolutionise treatment of neurological disorders as nanoparticles have the capacity to cross the BBB. Recently, researchers identified the neuroprotective potential of the protein S100A4.

During the course of the project NANONEUROPROTECTION (Nanomaterials for treatment of neurodegenerative disorders), scientists employed cutting edge techniques to characterise neuroprotective pathways and design neuroprotectant drugs based on S100A4 and its peptide derivatives – H3 and H6.

Tests on cell models of neurodegeneration revealed that S100A4, H3 and H6 had robust neuroprotective effects. Researchers also found them suitable for further development as drugs for neurological diseases.

A key finding, researchers identified a novel pro-survival pathway and proved that the S100-ErbB axis is involved in multiple aspects of neuroprotection. ErbB are neuronal receptors that have been linked to epilepsy, schizophrenia, Alzheimer's and Parkinson's diseases. Via several neurotoxicity models, they demonstrated that S100A4 directly binds to ErbB and activates pro-survival messengers. The expression of S100A4 and ErbB were correlated in brain injury in rodent models.

Another major development with great promise is the fabrication of spherical gold nanoparticles and gold plasmonic nanostars (AuNS) along with a nanoparticle delivery platform. AuNS, with its multispike morphology, demonstrated better access and supporting surface for attachment of biosensors or neuroactive agents. Researchers further optimised their functionalisation for improved delivery of S100 neuroprotectants and pilot data revealed their ability to cross the BBB.

The costs associated with neurodegenerative disorders such as stroke, epilepsy and Parkinson's disease amounts to hundreds of billions of euros annually in Europe alone. The NANONEUROPROTECTION study has opened up avenues for the development of neurotrophic S100-targeted nanoparticles that have minimal side effects. Flexibility in functionalisation could also be exploited to incorporate MRI-active compounds such as iron oxide to combine imaging with therapy.

Related information

Keywords

Neuroregeneration, neurodegenerative disorders, BBB, S100A4, NANONEUROPROTECTION, gold plasmonic nanostars, neuroprotective peptides
Record Number: 190752 / Last updated on: 2016-12-20
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