form various types of aggregates, such as oligomers, amorphous aggregates, and immature and mature fibers, depending on conditions and other molecular interactions [21-23]. The sequential conversion of water soluble A peptide monomers to intermediate toxic oligomers and large metastable -pleated amyloids have been proposed to understand the mechanistic approach for AD. The structural plasticity of unfolded A monomers to adopt transient oligomers also been investigated to confer their neurotoxicity
Dysbindin-1 promotes Drp1 oligomerization Mitochondrial fission requires dynamin-related protein 1 (Drp1). Drp1 is a large GTPase that can assemble into oligomers with enhanced GTPase activity. Drp1 is predominantly located in the cytosol and can be recruited to mitochondria to mediate mitochondrial fission by forming an oligomeric ring around the mitochondrial tubule to constrict and sever mitochondrial outer membranes 38-43. Having found that dysbindin-1 regulates mitochondrial fission, we proceeded
B30001 Assignment (Hatters) - Transthyretin Benjamin Andrikopoulos 759192 Introduction to TTR: Transthyretin (TTR) is a protein in the blood (serum) and cerebrospinal fluid of humans that functions in the transport of the thyroid hormone thyroxine (T4) and retinol (also known as Vitamin A1). [1] It is secreted by the liver into the blood and by the choroid plexus into the cerebrospinal fluid. [2] Studies have shown that as less than 1% of TTR 's T4-binding sites (T4BS) in the blood are in use
The calculated values for the HOMO and LUMO energies of all the homo- and co-oligomers at the B3LYP/6-31G(d,p) level of theory are given in Table S2. The results obtained showed that the co-polymerization of ANI with AAQ destabilized the HOMO and LUMO energy levels. Delocalization of π-electrons along an oligomer backbone can lead to a satisfactory resonance system, and improves its stabilization. The extended aromatic structure corresponds to the narrow band gap energy (Eg) defined as Eg = ELUMO
insulin in the peripheral tissues. Beta cell dysfunctioning decrease the release of amylin and insulin in response to increased blood glucose levels and this is thought to be affected by misfolded amylin proteins where the cytotoxicity from amylin oligomers affects the function of islet beta cells via several mechanisms and affecting the signaling pathway and apoptosis of beta cells. Introduction: There are 2 major types of diabetes in humans which revolves around the control of blood sugar level.
The protein misfolding induces structural conversion of a soluble protein to insoluble amyloids through self-assembling. The protein aggregation induces the loss of biological function and gain of disease and is well connected to several diseases such as neurodegenerative disorders, prion diseases and type-II diabetes. Several studies have been carried out to elucidate the role of protein misfolding and aggregation in the pathogenesis of a number of protein conformational diseases (ref). Among several
The spontaneous self-aggregation of Aβ into multiple coexisting physical forms, including oligomers (two to six peptides), leads to their coalescence into intermediate assemblies. In addition to this, β-amyloid can also grow into fibrils, which arrange themselves into β-pleated sheets to form the insoluble fibers of advanced amyloid plaques. Soluble oligomers and intermediate amyloids are the most neurotoxic forms of Aβ. In brain-slice preparations, synapses are toxified by
A hallmark feature of Alzheimers is the presence of Ab and tau phenotypes…. n Subsequent studies in animal models for insulin resistance, AD, or both, have established that insulin resistance exacerbates Aβ and tau phenotypes including enhanced Aβ 42/40 ratio, total tau, and hyperphosphorylated tau (Ho et al., 2004; Lester-Coll et al., 2006; Li et al., 2007; Masciopinto et al., 2012; Plaschke et al., 2010; Qu et al., 2011; Searcy et al., 2012; Takeda et al., 2010) and AD amyloidosis models exhibit
The monolignols are incorporated into lignin in the form of phenylpropanoids, such as guaiacyl (G) (Coniferyl alcohol), syringyl (S) (Sinapyl alcohol), and p-hydroxyphenyl (H) (p-Coumaryl alcohol). In general gymnosperm are composed mainly of G-units with little amount of H-units, and angiosperm dicot lignins of G- and S-units, but there are some exception (Uzal et al., 2009). Furthermore, lignin can be dissimilar among cell types and even at the level of individual cell wall layers, as revealed
Alzheimer’s disease is a progressive mental deterioration that can happen in middle or old age, due to generalized degeneration of the brain. Alzheimer’s disease is one form of dementia that gets harmful over time. Dementia is a loss of brain function that occurs with other diseases such as Alzheimer’s. Scientists believe that Alzheimer’s disease results from genetics, lifestyle, and environmental factors that impact the brain. Alzheimer’s disease damages and kills brain cells and it also leads