The AβA2V Paradigm: From Molecular Insights to Therapeutic Strategies in Alzheimer's disease and primary tauopathies.

Alzheimer's disease, the leading cause of dementia globally, represents an unresolved clinical challenge due to its complex pathogenesis and the absence of effective treatments. Considering the multifactorial etiology of the disease, mainly characterized by the accumulation of amyloid β plaques and neurofibrillary tangles of tau protein, we discuss the A673V mutation in the gene coding for the amyloid precursor protein, which is associated with the familial form of Alzheimer's disease in a homozygous state. The mutation offers new insights into the molecular mechanisms of the disease, particularly regarding the contrasting roles of the A2V and A2T mutations in amyloid β peptide aggregation and toxicity.

ATR and CDK4/6 inhibition target the growth of methotrexate-resistant choriocarcinoma.

Low-risk gestational trophoblastic neoplasia including choriocarcinoma is often effectively treated with Methotrexate (MTX) as a first line therapy. However, MTX resistance (MTX-R) occurs in at least ≈33% of cases. This can sometimes be salvaged with actinomycin-D but often requires more toxic combination chemotherapy.

Association between vitamin content, plant morphology and geographical origin in a worldwide collection of the orphan crop Gynandropsis gynandra (Cleomaceae).

The variability in nutrient content and morphology in Gynandropsis gynandra is associated with the geographic origin of the accessions and provides a basis for breeding for higher levels of vitamin C, carotenoids or tocopherols in higher-yielding cultivars. We examined the variation in carotenoids, tocopherols and ascorbic acid as well as morphological traits in a worldwide germplasm of 76 accessions of the orphan leafy vegetable Gynandropsis gynandra (Cleomaceae) using greenhouse experiments and high-performance liquid chromatography analysis. The levels of carotenoids and tocopherols accumulating in the leaves varied significantly across accessions and were linked with the geographical origin and morphological variation.

The A2V mutation as a new tool for hindering Aβ aggregation: A neutron and x-ray diffraction study.

We have described a novel C-to-T mutation in the APP gene that corresponds to an alanine to valine substitution at position 673 in APP (A673V), or position 2 of the amyloid-β (Aβ) sequence. This mutation is associated with the early onset of AD-type dementia in homozygous individuals, whereas it has a protective effect in the heterozygous state. Correspondingly, we observed differences in the aggregation properties of the wild-type and mutated Aβ peptides and their mixture.