The extracellular accumulation of β-amyloid peptide is a key trigger in the pathogenesis of Alzheimer's disease (AD). In humans, amyloid deposition precedes the appearance of intracellular inclusion pathology formed by cytosolic proteins such as Tau, α-synuclein and TDP-43. These secondary pathologies have not been observed in mice that model Alzheimer-type amyloidosis by expressing mutant amyl...

Alzheimer’s disease (AD) is the most common cause of age-related neurodegeneration and cognitive decline. AD more commonly occurs in females than males, so it necessary to consider new treatments specifically targeting this population. The present study investigated protective effects Begacestat (γ-secretase inhibitor-953, GSI-953) bone marrow-derived mesenchymal stem cells (BM-MSCs) during pre...

B-amyloid is the primary protein component of neuritic plaques, which are degenerative foci in brains of patients with Alzheimer's disease (AD). The effects of this naturally occurring B-amyloid on the cells of the central nervous system have not been completely understood. The effect of cytokines such as IL-IB, TNF-a, and IFN-y on astrocytic nitric oxide is well documented; however, the effect...

background: rna plays key role in many aspects of biological processes and its tertiary structure is critical for its biological function. rna secondary structure represents various significant portions of rna tertiary structure. since the biological function of rna is concluded indirectly from its primary structure, it would be important to analyze the relations between the rna sequences and t...

The membrane-active antifungal agent amphotericin B (AmB) is one of the few agents shown to slow the course of prion diseases in animals. Congo Red and other small molecules have been reported to directly inhibit amyloidogenesis in both prion and Alzheimer peptide model systems via specific binding. We propose that it is possible that AmB may act similarly to physically prevent conversion of th...

A hallmark of Alzheimer's, Huntington's and similar diseases is the assembly of proteins into amyloids rather than folding into their native state. There is an increasing appreciation that amyloids, under specific conditions, may be non-pathogenic. Here we show that amyloids form as a normal part of Xenopus oocyte development. Amyloids are detectable in the cytosol and the nucleus using an amyl...

Proteostasis refers to the regulation of the cellular concentration, folding, interactions and localization of each of the proteins that comprise the proteome. One essential element of proteostasis is the disposal of misfolded proteins by the cellular pathways of protein degradation. Lysosomes are an important site for the degradation of misfolded proteins, which are trafficked to this organell...

Apomyoglobin is an excellent example of a monomeric all α-helical globular protein whose folding pathway has been extensively studied and well characterized. Structural perturbation induced by denaturants or high temperature as well as amino acid substitution have been described to induce misfolding and, in some cases, aggregation. In this article, we review the molecular mechanism of the aggre...

We synthesized polypeptides corresponding to sequences encoded by normal and mutant alleles in the regions of codon 178 (Asp-->Asn) and codon 200 (Glu-->Lys) of the chromosome 20 amyloid gene that have been linked to familial Creutzfeldt-Jakob disease. Peptide suspensions from both regions spontaneously formed amyloid fibrils with different morphological characteristics and aggregation tendenci...

The permanganate method was applied to tissues from 35 cases of amyloidosis seen at the University Hospital. Kuala Lumpur. This method is based on the difference in affinity of various chemical types of amyloid for Congo red dye after treatment with potassium permanganate. Our findings agree with the concept that amyloid of largely immunoglobulin light chain composition (primary and myeloma amy...