In Vivo Assays for Amyloid-Related Diseases.

Amyloid-related diseases, such as Alzheimer's and Parkinson's disease, are devastating conditions caused by the accumulation of abnormal protein aggregates known as amyloid fibrils. While assays involving animal models are essential for understanding the pathogenesis and developing therapies, a wide array of standard analytical techniques exists to enhance our understanding of these disorders. These techniques provide valuable information on the formation and propagation of amyloid fibrils, as well as the pharmacokinetics and pharmacodynamics of candidate drugs. Despite ethical concerns surrounding animal use, animal models remain vital tools in the search for treatments. Regardless of the specific animal model chosen, the analytical methods used are usually standardized. Therefore, the main objective of this review is to categorize and outline the primary analytical methods used in in vivo assays for amyloid-related diseases, highlighting their critical role in furthering our understanding of these disorders and developing effective therapies.

Proximity-Induced Pharmacology for Amyloid-Related Diseases.

Proximity-induced pharmacology (PIP) for amyloid-related diseases is a cutting-edge approach to treating conditions such as Alzheimer's disease and other forms of dementia. By bringing small molecules close to amyloid-related proteins, these molecules can induce a plethora of effects that can break down pathogenic proteins and reduce the buildup of plaques. One of the most promising aspects of this drug discovery modality is that it can be used to target specific types of amyloid proteins, such as the beta-amyloid protein that is commonly associated with Alzheimer's disease. This level of specificity could allow for more targeted and effective treatments. With ongoing research and development, it is hoped that these treatments can be refined and optimized to provide even greater benefits to patients. As our understanding of the underlying mechanisms of these diseases continues to grow, proximity-induced pharmacology treatments may become an increasingly important tool in the fight against dementia and other related conditions.

Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-ß Aggregation and Acetylcholinesterase-Amyloid Interaction.

One of the pathological hallmarks of Alzheimer's disease (AD) is the formation of amyloid-ß plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-ß aggregation, hence being complementary to the palliative treatment of cholinergic decline. Antiaggregation assays performed for apigenin and quercetin, which are polyphenolic compounds that exhibit inhibitory properties against the formation of amyloid plaques, reveal distinct inhibitory effects of these compounds on Aß40 aggregation in the presence and absence of AChE. Furthermore, the analysis of the amyloid fibers formed in the presence of these flavonoids suggests that the Aß40 aggregates present different quaternary structures, viz., smaller molecular assemblies are generated. In agreement with a noncompetitive inhibition of AChE, molecular modeling studies indicate that these effects may be due to the binding of apigenin and quercetin at the peripheral binding site of AChE. Since apigenin and quercetin can also reduce the generation of reactive oxygen species, the data achieved suggest that multitarget catechol-type compounds may be used for the simultaneous treatment of various biological hallmarks of AD.