Susanne Aileen Funke

University of Applied Sciences Coburg · Institut für Bioanalytik

Alzheimer disease (AD) is the most common progressive neurodegenerative disorder. AD causes enormous personal and economic burden to society as currently only limited palliative therapeutic options are available. The pathological hallmarks of the disease are extracellular plaques, composed of fibrillar amyloid-β (Aβ), and neurofibrillary tangles in...

Background Recent studies indicate that the administration of open-label placebos (OLP) can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of OLP treatments on pain, functional disability, and mobility in patients with arthritic knee pain. Methods Sixty patients...

Background Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder that mainly affects older adults. One of the pathological hallmarks of AD is abnormally aggregated Tau protein that forms fibrillar deposits in the brain. In AD, Tau pathology correlates strongly with clinical symptoms, cognitive dysfu...

Background Two hexapeptide motifs within Tau, designated PHF6* (275VQIINK280) and PHF6 (306VQIVYK311), are known to drive Tau aggregation, making them attractive targets for the development of Tau aggregation inhibitors for therapeutic options. Method Employing mirror‐image phage display with a large peptide library, we have identified PHF6* fibri...

Alzheimer’s disease and other tauopathies are associated with neurofibrillary tangles composed of Tau protein, as well as toxic Tau oligomers. Therefore, inhibitors of pathological Tau aggregation are potentially useful candidates for future therapies targeting Tauopathies. Two hexapeptides within Tau, designated PHF6* (275‐VQIINK‐280) and PHF6 (30...

A variety of neurodegenerative disorders, including Alzheimer disease (AD), are associated with neurofibrillary tangles composed of the tau protein, as well as toxic tau oligomers. Inhib-itors of pathological tau aggregation, interrupting tau self-assembly, might be useful for the development of therapeutics. Employing mirror image phage display wi...

ELISA experiment demonstrating the binding of the selected peptides, as well as of a positive control, to tau monomers and fibrils in 5 μg/mL concentration. As a negative control, PBS pH 7.4 containing 1% BSA was incubated in the wells instead of tau protein solution. After incubation with 20 μg/mL of the respective peptide wit FAM-label, a horsera...

Representative distribution of TD28-FAM in the N2aK18ΔK280 cell body after 4 days of incubation with 60 μM peptide. (A): Space-resolved confocal z-stack 1–20 over 10.2 μM, step size: 0.51 μM. d-peptide: FAM staining (green): exc. 488 nm, em. 520 nm; cell nuclei: TOPRO3 staining (red): exc. 633 nm, em. 660–670 nm. (B): panel 10 of z-stack shown in S...

This file includes supporting materials and methods for S1 and S4 Figs as well as supporting literature for S4 Fig. (DOCX)

Representative distribution of KNT-FAM in the N2aK18ΔK280 cell body after 4 days of incubation with 60 μM peptide. (A) Space-resolved confocal z-stack 1–20 over 9.2 μM, step size: 0.46 μM. d-peptide: FAM staining (green): exc. 488 nm, em. 520 nm; cell nuclei: TOPRO3 staining (red): exc. 633 nm, em. 660–670 nm. (B) panel 10 of z-stack shown in A; se...

Treatment of inducible N2aTauK18ΔK280 cells with d-peptides. The bar diagram shows the relative amount of Thioflavin S positive cells when treated with increasing amounts of the tested d-peptides for 4 days (entry #3–16), compared to the untreated control (entry #2, set to 100%, dashed line), as quantified by FACS. In the case of peptides APT and K...

[This corrects the article DOI: 10.1371/journal.pone.0147470.].

Protein misfolding and aggregation are fundamental features of the majority of neurodegenerative diseases, like Alzheimer's disease (AD), Parkinson's disease, frontotemporal dementia, and prion diseases. Proteinaceous deposits in the brain of the patient, e.g., amyloid plaques consisting of the amyloid-β (Aβ) peptide and tangles composed of tau pro...

The aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer's disease (AD). In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized d-e...

Alzheimer´s disease is the most prominent type of dementia and currently no causative treatment is available. According to recent studies, oligomeric species of the amyloid beta (Aβ) peptide appear to be the most toxic Aβ assemblies. Aβ monomers, however, may be not toxic per se and may even have a neuroprotective role. Here we describe a competiti...

Strong evidence exists for a central role of amyloid β-protein (Aβ) oligomers in the pathogenesis of Alzheimer's disease. We have developed a fast, reliable and robust in vitro assay, termed QIAD, to quantify the effect of any compound on the Aβ aggregate size distribution. Applying QIAD, we studied the effect of homotaurine, scyllo-inositol, EGCG,...

In this study, we characterized unexpected side-products in a commercially synthesized peptide with the sequence RPRTRLHTHRNR. This so-called peptide D3 was selected by mirror phage display against low molecular weight amyloid-beta-peptide (Abeta) associated with Alzheimer's disease. Capillary electrophoresis (CE) was the method of choice for struc...

Recent evidence suggests Alzheimer-Disease (AD) to be driven by aggregated Aß. Capitalizing on the mechanism of molecular mimicry and applying several selection layers, we screened peptide libraries for moieties inducing antibodies selectively reacting with Aß-aggregates. The technology identified a pool of peptide candidates; two, AFFITOPES AD01 a...

Amyloid fibrils such as Semen-Derived Enhancer of Viral Infection (SEVI) or amyloid-beta-peptide (Abeta) enhance HIV-1 attachment and entry. Inhibitors destroying or converting those fibrils into non-amyloidogenic aggregates effectively reduce viral infectivity. Thus, they seem to be suitable as therapeutic drugs expanding the current HIV-interveni...

It is widely believed that Alzheimer's disease pathogenesis is driven by the production and deposition of the amyloid-β peptide (Aβ) in the brain. In this study, we employ a combination of in silico and in vitro approaches to investigate the inhibitory properties of selected arginine-rich D-enantiomeric peptides (D-peptides) against amyloid aggrega...

Agents for treating Alzheimer's disease comprising a peptide according to sequence no. 1 which binds to Abeta oligomers and thus results in the healing or alleviation of Alzheimer's disease. In further embodiments peptides are provided which contain a sequence no. 1, but have preceding sequence sections which allow the peptide to be secreted. For t...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with devastating effects. Currently, therapeutic options are limited to symptomatic treatment. For more than a decade, research focused on immunotherapy for the causal treatment of AD. However, clinical trials with active immunization using Aβ encountered severe complications, for...

The development of Alzheimer's disease (AD), a leading cause of dementia in the elderly, is characterised by brain neurons degeneration, which according to recent evidence results mainly from prefibrillar amyloid-β peptide (Aβ) assemblies. Structural and mechanistic aspects of these neurotoxic oligomeric provide an important basis for the design of...

Recent studies indicate that small amyloid-β peptide (Aβ) oligomers are the major toxic species responsible for development and progression of Alzheimer's disease (AD). Therefore, we suggest that the number of Aβ oligomers in body fluids is the most direct and relevant biomarker for AD. Determination of the Aβ oligomer content of cerebrospinal flui...

One of the characteristic pathological hallmarks of Alzheimer's disease (AD) is neuritic plaques. The sequence of events leading to deposition of amyloid-β (Aβ) peptides in plaques is not clear. Here we investigate the effects of D3, an Aβ oligomer directed D-enantiomeric peptide that was obtained from a mirror image phage display selection against...

The aggregation of the Aβ plays a fundamental role in the pathol. of AD. Recently, N-terminally modified Aβ species, pE-Aβ, have been described as major constituents of Aβ deposits in the brains of AD patients. PE-Aβ has an increased aggregation propensity and shows increased toxicity compared with Aβ1-40 and Aβ1-42. High-resoln. NMR spectroscopy w...

Alzheimer's disease (AD) is a devastating disease affecting predominantly the aging population. One of the characteristic pathological hallmarks of AD are neuritic plaques, consisting of amyloid-β peptide (Aβ). While there has been some advancement in diagnostic classification of AD patients according to their clinical severity, no fully reliable m...

One of the two characteristic pathological hallmarks of Alzheimer's disease (AD) are neuritic plaques. The sequence of events leading to the extracellular deposition of amyloid β (Aβ) peptides in plaques or in diffuse deposits is not clear. Here we investigate the relationship between aggregation and deposition of Aβ by using peptides that bind to...

Peptides are attracting increasing attention as therapeutics. D-enantiomeric peptides are remarkably resistant to in vivo proteolysis and elicit low immunogenic responses when compared with the respective L-peptides. Therefore, D-peptides can serve as therapeutic and early diagnosis agents for drug development. Here we discuss the application of mi...

Alzheimer's disease (AD) is the most common cause of dementia in elderly people, and age is the major nongenetic risk factor for sporadic AD. A hallmark of AD is the accumulation of amyloid in the brain, which is composed mainly of the amyloid beta-peptide (Aβ) in the form of oligomers and fibrils. However, how aging induces Aβ aggregation is not y...

A key feature of Alzheimer disease (AD) is the pathologic self-association of the amyloid-β (Aβ) peptide, leading to the formation of diffusible toxic Aβ oligomers and extracellular amyloid plaques. Next to extracellular Aβ, intraneuronal Aβ has important pathological functions in AD. Agents that specifically interfere with the oligomerization proc...

Parkinson disease (PD) is one of the most common age-related neurodegenerative diseases associated with motor deficiencies in humans. The symptoms are caused by the death of dopaminergic neurons in the brain, which is accompanied by the misfolding and aggregation of the protein α-synuclein. Diagnosis is based on the incidence of clinical symptoms,...

Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia. Today, only palliative therapies are available. The pathological hallmarks of AD are the presence of neurofibrillary tangles and amyloid plaques, mainly composed of the amyloid-β peptide (Aβ), in the brains of the patients. Several lines of e...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with devastating effects. The greatest risk factor to develop AD is age. Today, only symptomatic therapies are available. Additionally, AD can be diagnosed with certainty only post mortem, whereas the diagnosis "probable AD" can be established earliest when severe clinical symptom...

Alzheimer's disease (AD) is the most common cause of dementia in elderly people, and age is the major nongenetic risk factor for sporadic AD. A hallmark of AD is the accumulation of amyloid in the brain, which is composed mainly of the amyloid beta-peptide (Ab) in the form of oligomers and fibrils. However, how aging induces Ab aggregation is not y...

Today, the diagnosis of Alzheimer's disease (AD) is based on the identification of symptoms like dementia and other clinical indications. Cerebrospinal fluid (CSF) biomarkers like the level of amyloid-β 1-42 (Aβ42), which is lower in AD patients than in controls, or the levels of total Tau and phosphorylated Tau, which are enhanced, are supposed to...

The diagnosis of probable Alzheimer's disease (AD) can be established premortem based on clinical criteria like neuropsychological tests. Post mortem, specific neuropathological changes like amyloid plaques define AD. However, the standard criteria based on medical history and mental status examinations do not take into account the long preclinical...

Mehr als die Summe der Teile: Neuartige Hybridsubstanzen bestehen aus einem organischen, β-Faltblatt-brechenden Teil und einem die Zielsubstanz (Aβ) erkennenden, D-enantiomeren Peptidteil (siehe Bild). Die Substanzen wurden chemisch synthetisiert und mit verschiedenen Techniken charakterisiert. Sie vereinen rationales Design mit Substanzselektion a...

More than the sum of its parts: Novel hybrid compounds consisting of an organic β-sheet-breaking moiety and a signaling, D-enantiomeric Aβ-recognizing peptide moiety have been designed (see picture). The compounds, which were chemically synthesized and characterized by several techniques, combine rational design and drug selection from libraries an...

Several lines of evidence suggest that the amyloid-β-peptide (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). Not only Aβ fibrils but also small soluble Aβ oligomers in particular are suspected to be the major toxic species responsible for disease development and progression. The present study reports on in vitro and in vi...

Protein-ligand interactions characterise and govern the current state and fate of a living cell. The specificity of proteins is mainly determined by the relative affinities to each potential ligand. To investigate the consequences and potentials of ligands with increased specificity in comparison with ligands optimised solely for affinity, it was n...

Previously, two D-enantiomeric amino acid peptides, D1 and D3, which specifically bind to the amyloid-beta peptide Abeta(1-42), were identified by phage display selection. To assess the diagnostic and therapeutic potentials of D1 and D3 for the diagnosis and treatment of Alzheimer disease, the blood-brain barrier transport of these D-peptides was q...

Aging is the most significant risk factor for Alzheimer disease (AD). The pathological hallmark of AD is the accumulation of aggregated amyloid-beta (Abeta) forms and insoluble plaques, mainly composed of Abeta, in the brain of the patient. Recently, we reported on the selection of D-enantiomeric, Abeta-binding peptides D1 and D3. D1 was selected a...

Today, Alzheimer disease (AD) can be diagnosed with certainty only post mortem. A biomarker method for early diagnosis of AD is urgently needed. Abeta aggregates are directly involved in AD progression and therefore might be useful as biomarker in body fluids. We have developed an ultrasensitive assay system for the detection of Abeta aggregates in...

Mirror image phage display is a straightforward approach to identify new potentially therapeutically active D-enantiomeric peptides. Such D-peptides are more resistant to proteolytic degradation compared to L-peptides. In this review, several examples of mirror image phage display derived D-peptides with therapeutical potential are introduced and d...

N-Terminally truncated and pyroglutamate (pGlu) modified amyloid beta (Abeta) peptides are major constituents of amyloid deposits in sporadic and inherited Alzheimer's disease (AD). Formation of pGlu at the N-terminus confers resistance against cleavage by most aminopeptidases, increases toxicity of the peptides, and may seed Abeta aggregate format...

Today, the most reliable diagnosis for Alzheimer's disease (AD) is the post mortem identification of amyloid plaques, consisting of the Amyloid-beta (Abeta) peptide, (and neurofibrillary tangles) in the brain of the patient. Great efforts are being made to identify reliable biomarkers for AD that are suitable for minimal invasive early diagnosis an...

Today, the most reliable diagnosis for Alzheimer's disease (AD) is the post mortem identification of amyloid plaques, consisting of the Amyloid-β (Aβ) peptide, (and neurofibrillary tangles) in the brain of the patient. Great efforts are being made to identify reliable biomarkers for AD that are suitable for minimal invasive early diagnosis and prog...

Soluble amyloid beta(1-42) (A beta(1-42)) peptide has recently been assigned a key role in early Alzheimer's disease (AD) pathophysiology accounting for synaptic dysfunction before amyloid plaque formation and neurodegeneration can occur. Following sublethal A beta(1-42) administration, we observed an acute but transient reduction of the spike and...

Plaque visualisation: We identified three different D-enantiomeric peptides that bind to Alzheimer's amyloid β (Aβ1-42). As there is currently no definitive pre-mortem diagnosis for Alzheimer's disease, we investigated the peptides' suitability as molecular probes for in vivo imaging in transgenic mouse models. One of the characteristic pathologica...

(Figure Presented) Alzheimer's disease (AD) is a progressive neurodegenerative disorder, affecting more than 20 million people world-wide. Only palliative therapies are available today. We identified a novel D-enantiomeric amino acid peptide "D3" with significant Aβ disaggregation and Aβ aggregation inhibiting properties in vitro an in vivo. It inh...

Prion diseases, Alzheimer's disease, and Parkinson's disease are age-related neurodegenerative diseases that are characterized by the formation of protein aggregates during the progress of the disease. Although it is still not known whether these aggregates are causative for, or symptoms of, the disease. Many studies show that aggregates or even ol...

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia. Aging is among the most significant risk factors. Today, AD can be diagnosed with certainty only post mortem, detecting insoluble beta-amyloid peptide (Abeta) aggregates in the patient's brain tissue. We have developed an ultrasensitive assay for...

Neurodegenerative diseases like Alzheimer's disease (AD), priori diseases and others are progressive and lethal. High-molecular weight aggregates of the Amyloid-β-peptides (Aβ) or of the misfolded prion protein (PrP) are found in patients afflicted by AD or prion diseases, respectively. Despite of many attempts, neither a therapy for recovery, nor...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Today, AD can be diagnosed with certainty only post-mortem, by histopathologic staining of Abeta plaques and neurofibrillary tangles in brain tissue sections. We have developed an ultra-sensitive assay potentially suitable for early and non-i...

The amyloid cascade hypothesis assigns the amyloid-beta peptide (Abeta) a central role in the pathogenesis of Alzheimer's disease (AD). Although there are strong efforts to biophysically characterize formation of Abeta aggregates and fibrils, as well as their prevention, progress is still severly hampered by the availability of tens of milligrams o...

Hitherto accredited prion tests use the PK resistance of PrP(Sc), the pathogenic isoform of the prion protein, as a marker for the disease. Because of variations in the amount of disease-related aggregated PrP, which is not PK-resistant, these prion tests offer only limited sensitivity. Therefore, a prion detection method that does not rely on PK d...