Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

With a significant proportion of the global population growing older (>60 years), the low success rates of current diagnoses for early neurodegeneration signs are disappointing. Early detection of Alzheimer's disease (AD) can improve acclimatization and quality of life for patients in their...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bhargy Sharma, Joanes Grandjean, Margaret Phillips, Ambrish Kumar, Francesca Mandino, Ling Yun Yeow, Kimberly Jia Yi Low, Vikas Nandwana, Vinayak P. Dravid, Xing Bengang, Sierin Lim, Konstantin Pervushin
Formato:	article
Lenguaje:	EN
Publicado:	Wiley-VCH 2021
Materias:	diagnostics iron-oxide nanoparticles lipocalin-type prostaglandin d synthase magnetic resonance imaging neuroprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/c97eb6ddadf94a1ca6e1e77964ae3582
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c97eb6ddadf94a1ca6e1e77964ae3582
record_format	dspace
spelling	oai:doaj.org-article:c97eb6ddadf94a1ca6e1e77964ae35822021-11-06T04:12:26ZLipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice2699-930710.1002/anbr.202100019https://doaj.org/article/c97eb6ddadf94a1ca6e1e77964ae35822021-11-01T00:00:00Zhttps://doi.org/10.1002/anbr.202100019https://doaj.org/toc/2699-9307With a significant proportion of the global population growing older (>60 years), the low success rates of current diagnoses for early neurodegeneration signs are disappointing. Early detection of Alzheimer's disease (AD) can improve acclimatization and quality of life for patients in their later years. Endogenous proteins, such as the most abundant secreted protein in cerebrospinal fluid, lipocalin‐type prostaglandin d synthase (L‐PGDS), can bind the early toxic oligomers of amyloid β (Aβ) peptides implicated in AD and prevent their aggregation. Herein, the utility of L‐PGDS for detection of amyloids is demonstrated. L‐PGDS is conjugated with different iron‐oxide magnetic nanoparticles for contrast‐enhanced visualization using magnetic resonance imaging (MRI). These conjugates inhibit amyloid aggregation in vitro and improve viability in neuronal cells incubated with amyloid fibrils, showing a potential neuroprotective function. L‐PGDS‐ferritin conjugates, when administered intraventricularly, localize to AD‐associated amyloid‐rich regions in mice brain imaged using MRI and histological stains. As a proof‐of‐concept, it is demonstrated that L‐PGDS conjugates could reach the brain regions through non‐invasive intranasal administration. These conjugates are developed as the first entirely protein‐based nanoprobes for early detection of brain amyloids. The results of this study open a wider avenue for study of endogenous proteins as potential theranostics for AD.Bhargy SharmaJoanes GrandjeanMargaret PhillipsAmbrish KumarFrancesca MandinoLing Yun YeowKimberly Jia Yi LowVikas NandwanaVinayak P. DravidXing BengangSierin LimKonstantin PervushinWiley-VCHarticlediagnosticsiron-oxide nanoparticleslipocalin-type prostaglandin d synthasemagnetic resonance imagingneuroprotectionBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENAdvanced NanoBiomed Research, Vol 1, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diagnostics iron-oxide nanoparticles lipocalin-type prostaglandin d synthase magnetic resonance imaging neuroprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	diagnostics iron-oxide nanoparticles lipocalin-type prostaglandin d synthase magnetic resonance imaging neuroprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5 Bhargy Sharma Joanes Grandjean Margaret Phillips Ambrish Kumar Francesca Mandino Ling Yun Yeow Kimberly Jia Yi Low Vikas Nandwana Vinayak P. Dravid Xing Bengang Sierin Lim Konstantin Pervushin Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice
description	With a significant proportion of the global population growing older (>60 years), the low success rates of current diagnoses for early neurodegeneration signs are disappointing. Early detection of Alzheimer's disease (AD) can improve acclimatization and quality of life for patients in their later years. Endogenous proteins, such as the most abundant secreted protein in cerebrospinal fluid, lipocalin‐type prostaglandin d synthase (L‐PGDS), can bind the early toxic oligomers of amyloid β (Aβ) peptides implicated in AD and prevent their aggregation. Herein, the utility of L‐PGDS for detection of amyloids is demonstrated. L‐PGDS is conjugated with different iron‐oxide magnetic nanoparticles for contrast‐enhanced visualization using magnetic resonance imaging (MRI). These conjugates inhibit amyloid aggregation in vitro and improve viability in neuronal cells incubated with amyloid fibrils, showing a potential neuroprotective function. L‐PGDS‐ferritin conjugates, when administered intraventricularly, localize to AD‐associated amyloid‐rich regions in mice brain imaged using MRI and histological stains. As a proof‐of‐concept, it is demonstrated that L‐PGDS conjugates could reach the brain regions through non‐invasive intranasal administration. These conjugates are developed as the first entirely protein‐based nanoprobes for early detection of brain amyloids. The results of this study open a wider avenue for study of endogenous proteins as potential theranostics for AD.
format	article
author	Bhargy Sharma Joanes Grandjean Margaret Phillips Ambrish Kumar Francesca Mandino Ling Yun Yeow Kimberly Jia Yi Low Vikas Nandwana Vinayak P. Dravid Xing Bengang Sierin Lim Konstantin Pervushin
author_facet	Bhargy Sharma Joanes Grandjean Margaret Phillips Ambrish Kumar Francesca Mandino Ling Yun Yeow Kimberly Jia Yi Low Vikas Nandwana Vinayak P. Dravid Xing Bengang Sierin Lim Konstantin Pervushin
author_sort	Bhargy Sharma
title	Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice
title_short	Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice
title_full	Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice
title_fullStr	Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice
title_full_unstemmed	Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice
title_sort	lipocalin‐type prostaglandin d synthase conjugates as magnetic resonance imaging contrast agents for detecting amyloid β‐rich regions in the brain of live alzheimer's disease mice
publisher	Wiley-VCH
publishDate	2021
url	https://doaj.org/article/c97eb6ddadf94a1ca6e1e77964ae3582
work_keys_str_mv	AT bhargysharma lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT joanesgrandjean lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT margaretphillips lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT ambrishkumar lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT francescamandino lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT lingyunyeow lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT kimberlyjiayilow lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT vikasnandwana lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT vinayakpdravid lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT xingbengang lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT sierinlim lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice AT konstantinpervushin lipocalintypeprostaglandindsynthaseconjugatesasmagneticresonanceimagingcontrastagentsfordetectingamyloidbrichregionsinthebrainoflivealzheimersdiseasemice
_version_	1718443944488992768

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Ejemplares similares