The hunt for brain Aβ oligomers by peripherally circulating multi-functional nanoparticles: Potential therapeutic approach for Alzheimer disease

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• 作者：Simona Mancini ; MS^a ; ^{s.mancini6@campus.unimib.it" class="auth_mail" title="E-mail the corresponding author} ; Stefania Minniti ; MS^a ; ^{stefania.minniti1@libero.it" class="auth_mail" title="E-mail the corresponding author} ; Maria Gregori ; PhD^a ; ^{maria.gregori@unimib.it" class="auth_mail" title="E-mail the corresponding author} ; Giulio Sancini ; MS^a ; ^{giulio.sancini@unimib.it" class="auth_mail" title="E-mail the corresponding author} ; Alfredo Cagnotto ; MS^b ; ^{alfredo.cagnotto@marionegri.it" class="auth_mail" title="E-mail the corresponding author} ; Pierre-Olivier Couraud ; PhD^c ; ^{pierre-olivier.couraud@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Lara Ordó ; ñ ; ez-Gutié ; rrez ; MS^d ; ^{lordoniez@cbm.csic.es" class="auth_mail" title="E-mail the corresponding author} ; Francisco Wandosell ; PhD^d ; ^{fwandosell@cbm.csic.es" class="auth_mail" title="E-mail the corresponding author} ; Mario Salmona ; PhD^b ; ^{mario.salmona@marionegri.it" class="auth_mail" title="E-mail the corresponding author} ; Francesca Re ; PhD^a ; ^{francesca.re1@unimib.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：β-Amyloid oligomers ; Alzheimer disease ; Sink effect ; Nanoparticles ; Liposomes
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：12
• 期：1
• 页码：43-52
• 全文大小：717 K

文摘

We previously showed the ability of liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) to reduce brain Aβ in transgenic Alzheimer mice. Herein we investigated the efficacy of mApoE-PA-LIP to withdraw Aβ peptide in different aggregation forms from the brain, using a transwell cellular model of the blood–brain barrier and APP/PS1 mice. The spontaneous efflux of Aβ oligomers (Aβo), but not of Aβ fibrils, from the ‘brain’ side of the transwell was strongly enhanced (5-fold) in presence of mApoE-PA-LIP in the ‘blood’ compartment. This effect is due to a withdrawal of Aβo exerted by peripheral mApoE-PA-LIP by sink effect, because, when present in the brain side, they did not act as Aβo carrier and limit the oligomer efflux. In vivo peripheral administration of mApoE-PA-LIP significantly increased the plasma Aβ level, suggesting that Aβ-binding particles exploiting the sink effect can be used as a therapeutic strategy for Alzheimer disease.

From the Clinical Editor

Alzheimer disease (AD) at present is an incurable disease, which is thought to be caused by an accumulation of amyloid-β (Aβ) peptides in the brain. Many strategies in combating this disease have been focused on either the prevention or dissolving these peptides. In this article, the authors showed the ability of liposomes bi-functionalized with phosphatidic acid and with an ApoE- derived peptide to withdraw amyloid peptides from the brain. The data would help the future design of more novel treatment for Alzheimer disease.