RESUMO
Animal models are used to better understand the various mechanisms involved in the pathogenesis of diseases and explore potential pathways that will aid in discovering therapeutic targets. 3-Nitropropionic Acid (3-NPA) is a neurotoxin used to induce Huntington's disease (HD)-like symptoms in experimental animals. The 3-NPA is a fungus toxin that impairs the complex II (succinate dehydrogenase) activity of the mitochondria and reduces ATP synthesis, leading to excessive production of free radicals resulting in the degeneration of GABAergic medium spiny neurons (MSNs) in the striatum. This is characterized by motor impairments a key clinical manifestation of HD. 3-NPA has the potential to alter several cellular processes, including mitochondrial functions, oxidative stress, apoptosis, and neuroinflammation mimicking HD-like pathogenic conditions in animals. This review strives to provide a new insight towards the 3-NPA induced molecular dysfunctioning in developing an animal model of HD. Moreover, we summarise several preclinical studies that support the use of the 3-NPA-induced models for drug discovery and development in HD. This review is a collection of various articles that were published from 1977 to 2022 on Pubmed (1639), Web of Science (2139), and Scopus (2681), which are related to the 3-NPA induced animal model.
Assuntos
Doença de Huntington , Animais , Doença de Huntington/induzido quimicamente , Doença de Huntington/metabolismo , Neurotoxinas/toxicidade , Modelos Animais de Doenças , Nitrocompostos/toxicidade , Propionatos/toxicidade , Descoberta de DrogasRESUMO
From first principles calculations, we show that (InN)32 nanoparticles favor rock salt structure compared with wurtzite structure in bulk. A phase transition from wurtzite to rock salt structure is known to occur in bulk InN at 12.1 GPa and higher values of pressure for AlN and GaN. However, at the nanoscale we show that this structural transition takes place in (InN)32 without applying pressure. The charge asymmetry value "g" and cation/anion size ratio in InN describe very well this behavior. Similar studies on nanoparticles of AlN and GaN as well as a few other binary compounds such as MgS, AgI, ZnO, and CdSe, however, do not show such a transition. Our results suggest (InN)32 to be a unique candidate as further calculations on a few larger size (InN)n nanoparticles show that a filled cage (two shells) (InN)12@(InN)48 structure of (InN)60 has higher binding energy compared with a rock salt structure of (InN)64 leading to the conclusion that other 3D structures are likely to become favorable over rock salt structure for larger sizes.
RESUMO
The relative stability of Sc, Ti, and V encapsulating Ge(n) clusters in the size range n = 14-20 has been studied through first-principles electronic structure calculations based on density functional theory. Variations of the embedding energy, gap between the highest occupied and the lowest occupied molecular orbitals, ionization potential, vertical detachment energy, and electron affinity with cluster size have been calculated to identify clusters with enhanced stability. The enhanced stability of some clusters can be very well explained as due to the formation of a filled shell free-electron gas inside the Ge cages. For the first time, direct evidence of the formation of a free-electron gas is also presented. In some other clusters, enhanced stability is found to originate from geometric effects. Some clusters that may be expected to have enhanced stability from simple electron counting rules do not show that. These results provide new insights into the long-standing question of whether electron counting rules can explain the relative stability of transition metal encapsulated semiconductor clusters and show that these clusters are too complex for such simple generalizations.
RESUMO
The interactions between multiwall carbon nanotubes (MWCNTs) and poly(diallyl dimethylammonium) chloride (PDDA) have been studied in the presence of different ionic and nonionic surfactants, such as sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), Tween 20, 40, 60, and 80, and Triton X-100. On the basis of scanning electron microscopy (SEM) results, the MWCNT/PDDA sample treated with Triton X-100 has been observed to show good dispersion of nanotubes. This is due to the π-π stacking between the benzene ring of Triton X-100 and the hexagonal carbon rings of nanotubes and better coating of PDDA on MWCNTs, as is confirmed by the Raman studies. Energy dispersive X-ray (EDX) spectroscopic data shows the presence of higher oxygen content in the MWCNTs/PDDA/Triton X-100 sample. The maximum upshift in the C1s peak position and down-shift in the N1s peak position for the MWCNTs/PDDA/Triton X-100 sample has been observed from X-ray photoelectron spectroscopy (XPS) results and is due to the intermolecular charge transfer from carbon in MWCNTs to nitrogen in PDDA. The presence and nature of a surfactant in the MWCNTs/PDDA system has been found to affect their interactions. The above results suggest that the MWCNTs/PDDA/Triton X-100 system is suitable as a metal-free electrocatalyst for the oxygen reduction reaction (ORR) in fuel cells.