Selection of RNA Aptamers to the Alzheimer's Disease Amyloid Peptide

Ylera, Francisco; Lurz, Rudi; Erdmann, Volker A.; Fürste, Jens P.

doi:10.1006/bbrc.2002.6354

Cited by 108 publications

(88 citation statements)

References 24 publications

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“…Unfortunately, there has been little success in discovering aptamers that selectively bind to the monomeric or oligomeric forms of the Ab peptide. Rather, the majority of aptamers bind to the fibrillar form of Ab 1-40 or Ab 1-42 [73,74]. Selection of aptamers that bind to monomeric or oligomeric Ab peptide over other forms has proven to be particularly difficult due to the tendency of Ab to rapidly form insoluble aggregates.…”

Section: Aptamers For Alzheimer's Disease Treatmentmentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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Oligonucleotide aptamers are short, synthetic, single-stranded DNA or RNA able to recognize and bind to a multitude of targets ranging from small molecules to cells. Aptamers have emerged as valuable tools for fundamental research, clinical diagnosis, and therapy. Due to their small size, strong target affinity, lack of immunogenicity, and ease of chemical modification, aptamers are an attractive alternative to other molecular recognition elements, such as antibodies. Although it is a challenging environment, the central nervous system and related molecular targets present an exciting potential area for aptamer research. Aptamers hold promise for targeted drug delivery, diagnostics, and therapeutics. Here we review recent advances in aptamer research for neurotransmitter and neurotoxin targets, demyelinating disease and spinal cord injury, cerebrovascular disorders, pathologies related to protein aggregation (Alzheimer's, Parkinson's, and prions), brain cancer (glioblastomas and gliomas), and regulation of receptor function. Challenges and limitations posed by the blood brain barrier are described. Future perspectives for the application of aptamers to the central nervous system are also discussed.

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Section: Aptamers For Alzheimer's Disease Treatmentmentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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“…Aptamers have been obtained against amyloid beta (Ylera et al 2002;Takahashi et al 2009) and a prion (Weiss et al 1997;Proske et al 2002;Rhie et al 2003;Ogasawara et al 2007), both of which cause neurodegenerative disorders. However, aptamers against a-synuclein have not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Screening of DNA aptamer which binds to α-synuclein

2010

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Alpha-synuclein is a native, unfolded protein that causes several neurodegenerative diseases such as dementia with Lewy bodies and Parkinson's disease. We have now identified the first DNA aptamers against alpha-synuclein using native PAGE applied to the SELEX method. We call this aptamer "M5-15"; it is the alpha-synuclein-bound aptamer and was isolated after four cycles of screening. M5-15 is composed of three stem-loop structures that may play an important role in the binding to alpha-synuclein. Moreover, M5-15 specifically binds to the alpha-synuclein monomer and oligomer. We expect that this aptamer will become a useful tool in alpha-synuclein analysis and diagnosis.

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“…Indeed, RNA aptamers have already been generated against amyloid-like fibrils formed from A␤-(1-40) (36), and the disease-associated conformation of the prion protein (PrP) (37), the latter inhibiting conversion in vitro of monomeric PrP to the infectious scrapie form (PrP Sc ) (38 -40). Aptamers have distinct advantages over antibodies as potential therapeutics and diagnostics as they are significantly smaller, can be isolated rapidly in vitro and modified to include functional groups including chromophores, fluorophores, radiolabels, or novel functional groups.…”

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confidence: 99%

Production and Characterization of RNA Aptamers Specific for Amyloid Fibril Epitopes

Bunka

Mantle

Morten

et al. 2007

Journal of Biological Chemistry

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One of the most fascinating features of amyloid fibrils is their generic cross-␤ architecture that can be formed from many different and completely unrelated proteins. Nonetheless, amyloid fibrils with diverse structural and phenotypic properties can form, both in vivo and in vitro, from the same protein sequence. Here, we have exploited the power of RNA selection techniques to isolate small, structured, single-stranded RNA molecules known as aptamers that were targeted specifically to amyloidlike fibrils formed in vitro from ␤ 2 -microglobulin (␤ 2 m), the amyloid fibril protein associated with dialysis-related amyloidosis. The aptamers bind with high affinity (apparent K D ϳ nM) to ␤ 2 m fibrils with diverse morphologies generated under different conditions in vitro, as well as to amyloid fibrils isolated from tissues of dialysis-related amyloidosis patients, demonstrating that they can detect conserved epitopes between different fibrillar species of ␤ 2 m. Interestingly, the aptamers also recognize some other, but not all, amyloid fibrils generated in vitro or isolated from ex vivo sources. Based on these observations, we have shown that although amyloid fibrils share many common structural properties, they also have features that are unique to individual fibril types.A number of proteins and peptides undergo specific aggregation in vivo, leading to a range of pathological disorders, collectively known as amyloidoses (1, 2). These diseases are characterized by the deposition of normally soluble proteins or peptides into insoluble fibrillar arrays with a cross-␤ architecture (1, 2). About 30 different proteins have been identified as the fibrillar component of human amyloid deposits to date, although studies have shown that amyloid-like fibrils can be generated in vitro from virtually any protein sequence under suitable experimental conditions (3, 4). Remarkably, although amyloid and amyloid-like fibrils are formed from diverse precursor proteins with unrelated primary sequences and tertiary folds, they all adopt a cross-␤ molecular architecture, identified by x-ray fiber diffraction (5, 6) and bind a number of histological dyes, such as thioflavin T (ThT) and Congo Red (7,8), the latter showing a characteristic optical anisotropy with apple-green birefringence when viewed using cross-polarized light (9). The ubiquitous ability of amyloid fibrils to bind serum amyloid P component (10, 11), glycosaminoglycans and apolipoprotein E (12), together with the finding that antibodies (e.g. WO1) raised against A␤-(1-40) amyloid fibrils are also able to recognize amyloid fibrils formed from a wide variety of proteins and peptides, unrelated in sequence and structure (13), reinforces the view that amyloid fibrils possess a common core structure. Despite the immense interest in this field (1, 14), the mechanism of how normally soluble proteins or peptides are transformed into the ordered cross-␤ structure of amyloid is largely unknown, although partial denaturation of the native protein, or folding of disordered states to...

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Selection of RNA Aptamers to the Alzheimer's Disease Amyloid Peptide

Cited by 108 publications

References 24 publications

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

Screening of DNA aptamer which binds to α-synuclein

Production and Characterization of RNA Aptamers Specific for Amyloid Fibril Epitopes

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