Inhibition of amyloid formation of prion fragment (106-128) by polyphenolic compounds.

Prion diseases are characterized by the self-association and amyloid formation of misfolded prion proteins. Developing effective inhibitors of protein aggregation is critical for therapeutic intervention. In this study, we systematically evaluated a range of polyphenolic compounds as potential inhibitors of amyloid fibril formation of PrP(106-128), a prion fragment crucially involved in prion aggregation and propagation.

Alzheimer's Disease Immunotherapy: Current Strategies and Future Prospects.

Alzheimer's disease (AD) is an extremely complex and heterogeneous pathology influenced by many factors contributing to its onset and progression, including aging, amyloid-beta (Aβ) plaques, tau fibril accumulation, inflammation, etc. Despite promising advances in drug development, there is no cure for AD. Although there have been substantial advancements in understanding the pathogenesis of AD, there have been over 200 unsuccessful clinical trials in the past decade.

Effect of phospholipid liposomes on prion fragment (106-128) amyloid formation.

Misfolding and aggregation of cellular prion protein (PrP) is a major molecular process involved in the pathogenesis of prion diseases. Here, we studied the aggregation properties of a prion fragment peptide PrP(106-128). The results show that the peptide aggregates in a concentration-dependent manner in an aqueous solution and that the aggregation is sensitive to pH and the preformed amyloid seeds.

Effects of zinc and carnosine on aggregation kinetics of Amyloid-β40 peptide.

The accumulation and amyloid formation of amyloid-β (Aβ) peptides is closely associated with the pathology of Alzheimer's disease. The physiological environment wherein Aβ aggregation happens is crowded with a large variety of metal ions including Zn. In this study, we investigated the role of Zn in regulating the aggregation kinetics of Aβ40 peptide.

Tau liquid-liquid phase separation: At the crossroads of tau physiology and tauopathy.

Abnormal deposition of tau in neurons is a hallmark of Alzheimer's disease and several other neurodegenerative disorders. In the past decades, extensive efforts have been made to explore the mechanistic pathways underlying the development of tauopathies. Recently, the discovery of tau droplet formation by liquid-liquid phase separation (LLPS) has received a great deal of attention.

Mucin-Type -Glycosylation Proximal to β-Secretase Cleavage Site Affects APP Processing and Aggregation Fate.

The amyloid-β precursor protein (APP) undergoes proteolysis by β- and γ-secretases to form amyloid-β peptides (Aβ), which is a hallmark of Alzheimer's disease (AD). Recent findings suggest a possible role of -glycosylation on APP's proteolytic processing and subsequent fate for AD-related pathology. We have previously reported that Tyr--glycosylation and the Swedish mutation accelerate cleavage of APP model glycopeptides by β-secretase (amyloidogenic pathway) more than α-secretase (non-amyloidogenic pathway).

Therapeutic strategies for tauopathies and drug repurposing as a potential approach.

Tauopathies are neurodegenerative diseases characterized by the deposition of abnormal tau in the brain. To date, there are no disease-modifying therapies approved by the U.S.