{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:53:59Z","timestamp":1791942839499,"version":"4.3.4"},"reference-count":134,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AmyPore company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurodegenerative disorders are a major public health issue. Despite decades of research efforts, we are still seeking an efficient cure for these pathologies. The initial paradigm of large aggregates of amyloid proteins (amyloid plaques, Lewis bodies) as the root cause of Alzheimer\u2019s and Parkinson\u2019s diseases has been mostly dismissed. Instead, membrane-bound oligomers forming Ca2+-permeable amyloid pores are now considered appropriate targets for these diseases. Over the last 20 years, our group deciphered the molecular mechanisms of amyloid pore formation, which appeared to involve a common pathway for all amyloid proteins, including A\u03b2 (Alzheimer) and \u03b1-synuclein (Parkinson). We then designed a short peptide (AmyP53), which prevents amyloid pore formation by targeting gangliosides, the plasma membrane receptors of amyloid proteins. Herein, we show that aqueous solutions of AmyP53 are remarkably stable upon storage at temperatures up to 45 \u00b0C for several months. AmyP53 appeared to be more stable in whole blood than in plasma. Pharmacokinetics studies in rats demonstrated that the peptide can rapidly and safely reach the brain after intranasal administration. The data suggest both the direct transport of AmyP53 via the olfactory bulb (and\/or the trigeminal nerve) and an indirect transport via the circulation and the blood\u2013brain barrier. In vitro experiments confirmed that AmyP53 is as active as cargo peptides in crossing the blood\u2013brain barrier, consistent with its amino acid sequence specificities and physicochemical properties. Overall, these data open a route for the use of a nasal spray formulation of AmyP53 for the prevention and\/or treatment of Alzheimer\u2019s and Parkinson\u2019s diseases in future clinical trials in humans.<\/jats:p>","DOI":"10.3390\/ijms232113383","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T03:11:21Z","timestamp":1667445081000},"page":"13383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["AmyP53, a Therapeutic Peptide Candidate for the Treatment of Alzheimer\u2019s and Parkinson\u2019s Disease: Safety, Stability, Pharmacokinetics Parameters and Nose-to Brain Delivery"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-7056","authenticated-orcid":false,"given":"Coralie","family":"Di Scala","sequence":"first","affiliation":[{"name":"Neuroscience Center\u2014HiLIFE, Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-2244","authenticated-orcid":false,"given":"Nicholas","family":"Armstrong","sequence":"additional","affiliation":[{"name":"IRD, APHM, MEPHI, IHU M\u00e9diterran\u00e9e Infection, Aix Marseille University, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Chahinian","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1072, Aix Marseille University, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Chabri\u00e8re","sequence":"additional","affiliation":[{"name":"IRD, APHM, MEPHI, IHU M\u00e9diterran\u00e9e Infection, Aix Marseille University, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-5521","authenticated-orcid":false,"given":"Jacques","family":"Fantini","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1072, Aix Marseille University, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouara","family":"Yahi","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1072, Aix Marseille University, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3934\/Neuroscience.2021005","article-title":"The biological pathways of Alzheimer disease: A review","volume":"8","author":"Rinaldi","year":"2021","journal-title":"AIMS Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, regional, and national burden of neurological disorders, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Collaborators","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/geront\/37.2.150","article-title":"Aging and Alzheimer\u2019s disease: Lessons from the Nun Study","volume":"37","author":"Snowdon","year":"1997","journal-title":"Gerontologist"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0022-510X(68)90154-8","article-title":"Observations on the brains of non-demented old people","volume":"7","author":"Tomlinson","year":"1968","journal-title":"J. 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