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 ( ). Many lines of evidence suggest that prions ( ) act both as a template for this conversion and as a neurotoxic agent causing neuronal dysfunction and cell death. As such, 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. 1. Introduction Neurodegenerative diseases are a medical, social, and economic problem of paramount importance in developed countries. Besides the fact that their etiology is generally unknown, developing therapeutic and diagnostic interventions for diseases of the central nervous system (CNS) is further complicated by the impermeability of the blood brain barrier (BBB). Thus, Alzheimer’s disease (AD) and prion diseases are still not curable with drugs, and only in 2012 [1–3] positron emission tomography (PET) imaging probes have been included in the AD diagnostic armamentarium. In recent years, the close cooperation between drug delivery/treatment and molecular imaging disciplines has resulted in a relatively new branch of knowledge, known as theranostics. The term theranostics was coined to indicate the concomitant therapeutic and diagnostic properties in a single agent. The purpose of theranostics is to optimize the efficacy and safety of therapy, as well as to streamline the entire drug development process. Several exciting examples of theranostic systems have now been reported in the literature for the treatment of cancer [4], atherosclerosis [5], and gene delivery [6], but very few examples are reported in the neuropathological
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