Natural compounds as inhibitors of transthyretin amyloidosis and neuroprotective agents: analysis of structural data for future drug design

Abstract

Natural compounds, such as plant and fruit extracts have shown neuroprotective effect against neurodegenerative diseases. It has been reported that several natural compounds binding to transthyretin (TTR) can be useful in amyloidosis prevention. TTR is a transporter protein that under physiological condition carries thyroxine (T₄) and retinol in plasma and in cerebrospinal fluid (CSF); it also has a neuroprotective role against Alzheimer’s disease (AD). However, TTR also is an amyloidogenic protein responsible for familial amyloid polyneuropathy (FAP) and familial amyloid cardiomyopathy (FAC). The TTR amyloidogenic potential is speeded up by several point mutations. One therapeutic strategy against TTR amyloidosis is the stabilisation of the native tetramer by natural compounds and small molecules. In this review, we examine the natural products that, starting from 2012 to present, have been studied as a stabiliser of TTR tetramer. In particular, we discussed the chemical and structural features which will be helpful for future drug design of new TTR stabilisers.

Keywords:

• Natural compounds
• transthyretin amyloid diseases
• neuroprotection
• X-ray structure analysis
• drug discovery

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by the PRIN 2017 grant prot. 2017SNRXH3 from the Italian Ministry of Education, University and Research (MIUR).