Recent progress in fluorescent probes for transthyretin sensing

Amyloidosis is a group of rare disorders caused by the deposition of protein aggregates in body tissues. To date, more than 20 human proteins are known to cause amyloidosis, the most common ones being immunoglobulins, beta-amyloid and transthyretin. Transthyretin (TTR) is mainly produced by the liver and it is involved in the transport of l-thyroxine and retinol. Transthyretin amyloidosis (ATTR) mainly manifests as a polyneuropathy that can lead to nerve damage (ATTR-PN), or as a cardiomyopathy that can lead to heart failure (ATTR-CM). Under normal circumstances, TTR exists in serum as a soluble tetramer. The pathogenesis of ATTR is due to the abnormal dissociation of the tetramers and misfolding of unstable TTR molecules, followed by the formation of pathogenic amyloid deposits in the extracellular space of tissues and organs, which cause cytotoxicity and tissue damage. ATTR lacks specific clinical symptoms, and its diagnosis requires many inspection steps, long waiting periods and the collection of a large amount of information. In addition, the pathological examination is likely to damage the involved tissues. Early detection, diagnosis and treatment can have a significant impact on the management of ATTR and improve the life of patients. Since serum TTR can be quantified by using fluorescent probes, these probes could be used as a tool for the early diagnosis of ATTR. This approach promises excellent sensitivity, simplicity, rapid response, and cost-effectiveness. Many fluorescent probes have been recently developed for selectively bind TTR in complex biological environments. These probes are highly fluorescent when bound to TTR while being mostly non-fluorescent when free in aqueous buffers. Here, we introduce the main characteristics of TTR and ATTR and present a summary of the newly reported fluorescent probes for TTR, along with more traditional ones, including their structural design, optical properties, chemical properties and imaging characteristics.