Outcomes and Health Care Service Use in Adults 50 Years or Older With and Without Multiple Sclerosis: A 6-Year Observational Analysis.

Background: Multiple sclerosis (MS) typically presents in young adulthood. Recent data show the highest prevalence of MS in people aged 55 to 64 years; however, there are limited studies of this population.

Methods: Administrative US claims data from IBM-Truven MarketScan commercial and Medicare databases (2011-2017) were analyzed.

Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies.

Objective: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy.

Methods: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control).

The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells.

Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145.

The histidine composition of the amyloid-β domain, but not the E1 copper binding domain, modulates β-secretase processing of amyloid-β protein precursor in Alzheimer's disease.

Amyloid-β protein precursor (AβPP) proteolysis by β- and γ-secretases generates neurotoxic amyloid-β (Aβ)-peptides in Alzheimer's disease (AD). We have investigated the role of histidine residues within the extracellular E1 copper binding and Aβ domains of AβPP in its proteolysis. By stably expressing histidine to alanine AβPP mutant constructs in SH-SY5Y cells, we show that mutations in the E1 copper binding domain had no impact on α- or β-secretase processing.

The amyloid precursor protein represses expression of acetylcholinesterase in neuronal cell lines.

The toxic role of amyloid β peptides in Alzheimer's disease is well documented. Their generation is via sequential β- and γ-secretase cleavage of the membrane-bound amyloid precursor protein (APP). Other APP metabolites include the soluble ectodomains sAPPα and sAPPβ and also the amyloid precursor protein intracellular domain (AICD).

Zinc metalloproteinases and amyloid Beta-Peptide metabolism: the positive side of proteolysis in Alzheimer's disease.

Alzheimer's disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (Aβ-)peptides in the brain causing progressive neuronal death. Aβ-peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to this detrimental "amyloidogenic" form of proteolysis, a range of zinc metalloproteinases can process APP via an alternative "nonamyloidogenic" pathway in which the protein is cleaved within its Aβ region thereby precluding the formation of intact Aβ-peptides.