Small-Molecule Theranostic Probes: A Promising Future in Neurodegenerative Diseases

Abstract

Prion diseases are fatal neurodegenerative illnesses, which include Creutzfeldt-Jakob disease in humans and scrapie, chronic wasting disease, and bovine spongiform encephalopathy in animals. They are caused by unconventional infectious agents consisting primarily of misfolded, aggregated, β-sheet-rich isoforms, denoted prions, of the physiological cellular prion protein (PrPC). Many lines of evidence suggest that prions (PrPSc) act both as a template for this conversion and as a neurotoxic agent causing neuronal dysfunction and cell death. As such, PrPSc may be considered as both a neuropathological hallmark of the disease and a therapeutic target. Several diagnostic imaging probes have been developed to monitor cerebral amyloid lesions in patients with neurodegenerative disorders (such as Alzheimer's disease, Parkinson's disease, and prion disease). Examples of these probes are Congo red, thioflavin T, and their derivatives. We synthesized a series of styryl derivatives, denoted theranostics, and studied their therapeutic and/or diagnostic potentials. Here we review the salient traits of these small molecules that are able to detect and modulate aggregated forms of several proteins involved in protein misfolding diseases. We then highlight the importance of further studies for their practical implications in therapy and diagnostics.

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

“…In addition, congo red can inhibit amyloid toxicity by the blockade of Ca 2+ permeable amyloid-formed ion channels [6,7] . Congo red has demonstrated neuroprotective effects in a variety of models of neurodegenerative disorders, such as Alzheimer's, Parkinson's, Huntington's and prion disease [23] . Therefore, understanding the underlying mechanisms of congo red will be instructive for the design of future compounds to monitor and treat neurodegenerative diseases.…”

Multitarget Ligands and Theranostics: Sharpening the Medicinal Chemistry Sword Against Prion Diseases

“…Theranostic small molecules Brain amyloidogenic deposition is the main pathological hallmark of PrDs, which is believed to precede clinical symptoms by several years [106,107]. Therefore, imaging of fibrillar aggregates is particularly suitable to diagnose the onset of the disease in its early stage and monitor its progression [108]. On the other hand, as outlined above, amyloid fibrils have been shown to have therapeutic implications.…”

“…In addition, the incubation time of an experimental prion mouse model was prolonged when BSB was injected intravenously [120]. In this vein, amyloid ligands that showed concomitant capability of staining abnormal prion deposits and inhibiting prion replication were recently reviewed [108,121]. Thus, it seems convincible that PrP Sc binding compounds represent attractive candidates for monitoring the aggregation process and at the same time for therapeutic intervention.…”

Optimizing conditions for production of high levels of soluble recombinant human growth hormone using Taguchi method

“…Using of pituitary-derived hGH has been prohibited when its association with Creutzfeldt-Jakob disease was proved [2]. Although recombinant DNA technology has presented as a safe way of producing numerous products of rhGH in various heterologous systems, improper folding of the overexpressed proteins has been as an important limitation for the production of recombinant proteins in E. coli as well as formation of insoluble protein aggregates (inclusion bodies) in vivo.…”