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Protein misfolding diseases (PMDs) are chronic and progressive, with no effective therapy so far. Aggregation and misfolding of amyloidogenic proteins are closely associated with the onset and progression of PMDs, such as amyloid-β (Aβ) in Alzheimer's disease, α-Synuclein (α-Syn) in Parkinson's disease and human islet amyloid polypeptide (hIAPP) in type 2 diabetes. Inhibiting toxic aggregation of amyloidogenic proteins is regarded as a promising therapeutic approach in PMDs. The past decade has witnessed the rapid progresses of this field, dozens of inhibitors have been screened and verified in vitro and in vivo, demonstrating inhibitory effects against the aggregation and misfolding of amyloidogenic proteins, together with beneficial effects. Natural products are major sources of small molecule amyloid inhibitors, a number of natural derived compounds have been identified with great bioactivities and translational prospects. Here, we review the non-polyphenolic natural inhibitors that potentially applicable for PMDs treatment, along with their working mechanisms. Future directions are proposed for the development and clinical applications of these inhibitors., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The increased incidence of neurodegenerative diseases represents a huge challenge for societies. These diseases are characterized by neuronal death and include several different pathologies, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease and transmissible spongiform encephalopathies. Most of these pathologies are often associated with the aggregation of misfolded proteins, such as amyloid-ß, tau, α-synuclein, huntingtin and prion proteins. However, the precise mechanisms that lead to neuronal dysfunction and death in these diseases remain poorly understood. Nucleic acid aptamers represent a new class of ligands that could be useful to better understand these diseases and develop better diagnosis and therapy. In this review, several of these aptamers are presented as well as their applications for neurodegenerative diseases., (Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Alzheimer's disease characterized by misfolding, aggregation, and accumulation of amyloid fibrils in an insoluble form in the brain, is often known as amyloidosis. The process of aggregation follows a mechanism of seeded polymerization. For decades, a great number of failures in Alzheimer's disease (AD) drug development, with both small molecules and immunotherapies failing to establish a drug/placebo difference or having an unacceptable toxicity have led to the therapeutic research interest towards a group of anti-amyloidogenic compounds originated from plants called biophenols. A number of in vitro and in vivo studies have demonstrated that the plant biophenols bind with amyloid beta (Aβ) toxic oligomers and reducing the fibril formation and toxicity. The exact mechanism of biophenols action against Aβ toxicity is unknown, while studies have suggested the amyloid-binding affinity of biophenols affecting Aβ on various levels, e.g. by direct inhibiting fibril formation or steering oligomer formation into unstructured, inhibiting Aβ aggregation, and promoting nontoxic pathways. Furthermore, biophenols involved in the inhibition of Aβ progression (e.g., oxidative stress and neuroinflammation) and effecting the amyloid precursor protein processing through the direct or indirect inhibition of β-secretase (BACE-1), γ-secretase and/or activation of α-secretase. This critical review account for the biophenols as magic bullet targeting against Aβ, and simulation the results on how biophenols interact with the Aβ monomers and oligomers, highly desirable knowledge for predicting new efficient nutraceutical drugs., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)