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      BODIPY Dyes as Probes and Sensors to Study Amyloid-β-Related Processes

      review-article
      Biosensors
      MDPI
      amyloids, protein folding, Alzheimer’s disease, Aβ1-42, BODIPY, fluorescent dyes, environment-sensitive probes

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          Abstract

          Amyloid formation plays a major role in a number of neurodegenerative diseases, including Alzheimer’s disease. Amyloid-β peptides (Aβ) are one of the primary markers associated with this pathology. Aβ aggregates exhibit a diverse range of morphologies with distinct pathological activities. Recognition of the Aβ aggregates by using small molecule-based probes and sensors should not only enhance understanding of the underlying mechanisms of amyloid formation, but also facilitate the development of therapeutic strategies to interfere with amyloid neurotoxicity. BODIPY (boron dipyrrin) dyes are among the most versatile small molecule fluorophores. BODIPY scaffolds could be functionalized to tune their photophysical properties to the desired ranges as well as to adapt these dyes to various types of conditions and environments. Thus, BODIPY dyes could be viewed as unique platforms for the design of probes and sensors that are capable of detecting and tracking structural changes of various Aβ aggregates. This review summarizes currently available examples of BODIPY dyes that have been used to investigate conformational changes of Aβ peptides, self-assembly processes of Aβ, as well as Aβ interactions with various molecules.

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          Most cited references101

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          The amyloid hypothesis of Alzheimer's disease at 25 years

          Abstract Despite continuing debate about the amyloid β‐protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics worldwide support the concept that an imbalance between production and clearance of Aβ42 and related Aβ peptides is a very early, often initiating factor in Alzheimer's disease (AD). Confirmation that presenilin is the catalytic site of γ‐secretase has provided a linchpin: all dominant mutations causing early‐onset AD occur either in the substrate (amyloid precursor protein, APP) or the protease (presenilin) of the reaction that generates Aβ. Duplication of the wild‐type APP gene in Down's syndrome leads to Aβ deposits in the teens, followed by microgliosis, astrocytosis, and neurofibrillary tangles typical of AD. Apolipoprotein E4, which predisposes to AD in > 40% of cases, has been found to impair Aβ clearance from the brain. Soluble oligomers of Aβ42 isolated from AD patients' brains can decrease synapse number, inhibit long‐term potentiation, and enhance long‐term synaptic depression in rodent hippocampus, and injecting them into healthy rats impairs memory. The human oligomers also induce hyperphosphorylation of tau at AD‐relevant epitopes and cause neuritic dystrophy in cultured neurons. Crossing human APP with human tau transgenic mice enhances tau‐positive neurotoxicity. In humans, new studies show that low cerebrospinal fluid (CSF) Aβ42 and amyloid‐PET positivity precede other AD manifestations by many years. Most importantly, recent trials of three different Aβ antibodies (solanezumab, crenezumab, and aducanumab) have suggested a slowing of cognitive decline in post hoc analyses of mild AD subjects. Although many factors contribute to AD pathogenesis, Aβ dyshomeostasis has emerged as the most extensively validated and compelling therapeutic target.
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            Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases.

            A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.
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              The chemistry of fluorescent bodipy dyes: versatility unsurpassed.

              The world of organic luminophores has been confined for a long time to fairly standard biological labeling applications and to certain analytical tests. Recently, however, the field has undergone a major change of direction, driven by the dual needs to develop novel organic electronic materials and to fuel the rapidly emerging nanotechnologies. Among the many diverse fluorescent molecules, the Bodipy family, first developed as luminescent tags and laser dyes, has become a cornerstone for these new applications. The near future looks extremely bright for "porphyrin's little sister".
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                Author and article information

                Journal
                Biosensors (Basel)
                Biosensors (Basel)
                biosensors
                Biosensors
                MDPI
                2079-6374
                27 November 2020
                December 2020
                : 10
                : 12
                : 192
                Affiliations
                Department of Chemistry and Biochemistry, Texas Christian University, Fort Worth, TX 76129, USA; s.dzyuba@ 123456tcu.edu
                Article
                biosensors-10-00192
                10.3390/bios10120192
                7760207
                33260945
                58567cb8-de09-4ccf-849e-4277d6f6106a
                © 2020 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 November 2020
                : 26 November 2020
                Categories
                Review

                amyloids,protein folding,alzheimer’s disease,aβ1-42,bodipy,fluorescent dyes,environment-sensitive probes

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