Inhibition of protein misfolding and aggregation by natural phenolic compounds.

Cell Mol Life Sci. 2018 Oct;75(19):3521-3538. doi: 10.1007/s00018-018-2872-2. Epub 2018 Jul 20. Dhouafli Z1,2, Cuanalo-Contreras K3, Hayouni EA2, Mays CE3, Soto C3, Moreno-Gonzalez I4,5. Author information 1 Université de Tunis El Manar, Faculté des Sciences de Tunis, 2092, Tunis, Tunisia. 2 Laboratory of Aromatic and Medicinal Plants, Center of Biotechnology of Borj-Cédria, BP 901, 2050, Hammam-Lif, Tunisia. 3 The Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. 4 The Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Ines.M.Gonzalez@uth.tmc.edu. 5 Department of Cell Biology, Networking Research Center on Neurodegenerative Diseases (CIBERNED), Facultad Ciencias, Universidad de Malaga, Málaga, Spain. Ines.M.Gonzalez@uth.tmc.edu. Abstract Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer's and Parkinson's diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases. KEYWORDS: Aggregates; Alpha-synuclein; Alzheimer’s disease; Amylin; Amyloid beta; Amyloid inhibitors; Flavonoids; Misfolded proteins; Natural compounds; Parkinson’s disease; Polyphenols; Prion diseases; Protein misfolding disorders; Tau; Type 2 diabetes PMID: 30030591 DOI: 10.1007/s00018-018-2872-2 [Indexed for MEDLINE]