ArticleActa neuropathologica communications2014
Systemic delivery of P42 peptide: a new weapon to fight Huntington's disease.
Article in Acta neuropathologica communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- MALDI imaging mass spectrometry: an emerging tool in neurology.Metabolic brain disease · 2022Review
- Neurodegenerative Proteinopathies in the Proteoform Spectrum-Tools and Challenges.International journal of molecular sciences · 2021Review
- Imaging Mass Spectrometry: A New Tool to Assess Molecular Underpinnings of Neurodegeneration.Metabolites · 2019Review
- Lithium as a disease-modifying agent for prion diseases.Translational psychiatry · 2018Article
- A peptidylic inhibitor for neutralizing expandedRNA (New York, N.Y.) · 2018Article
- BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.Translational psychiatry · 2017Article
- The P42 peptide and Peptide-based therapies for Huntington's disease.Orphanet journal of rare diseases · 2016Review
- Tackling amyloidogenesis in Alzheimer's disease with A2V variants of Amyloid-β.Scientific reports · 2016Article
- Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty.Scientific reports · 2016Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn Huntington's disease (HD), the ratio between normal and mutant Huntingtin (polyQ-hHtt) is crucial in the onset and progression of the disease. As a result, addition of normal Htt was shown to improve polyQ-hHtt-induced defects. Therefore, we recently identified, within human Htt, a 23aa peptide (P42) that prevents aggregation and polyQ-hHtt-induced phenotypes in HD Drosophila model. In this report, we evaluated the therapeutic potential of P42 in a mammalian model of the disease, R6/2 mice.
resultsTo this end, we developed an original strategy for P42 delivery, combining the properties of the cell penetrating peptide TAT from HIV with a nanostructure-based drug delivery system (Aonys® technology), to form a water-in-oil microemulsion (referred to as NP42T) allowing non-invasive per mucosal buccal/rectal administration of P42. Using MALDI Imaging Mass Spectrometry, we verified the correct targeting of NP42T into the brain, after per mucosal administration. We then evaluated the effects of NP42T in R6/2 mice. We found that P42 (and/or derivatives) are delivered into the brain and target most of the cells, including the neurons of the striatum. Buccal/rectal daily administrations of NP42T microemulsion allowed a clear improvement of behavioural HD-associated defects (foot-clasping, rotarod and body weights), and of several histological markers (aggregation, astrogliosis or ventricular areas) recorded on brain sections.
conclusionsThese data demonstrate that NP42T presents an unprecedented protective effect, and highlight a new therapeutic strategy for HD, associating an efficient peptide with a powerful delivery technology.
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