Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist treatment.

Entorhinal cortex lesioning (ECL) causes an extensive deafferentation of the hippocampus that is classically followed by a compensatory reinnervation, where apolipoprotein E, the main extracellular lipid-carrier in the CNS, has been shown to play a crucial role by shuttling cholesterol to reconstructing neurons terminals. Hence, we investigated whether the ATP-binding cassette (ABC) transporters -A1 and -G1, known to regulate cellular cholesterol efflux and lipidation of the apolipoprotein E-containing lipoprotein complex are actively involved in this context of brain׳s plastic response to neurodegeneration and deafferentation. We assessed ABCA1 and ABCG1 mRNA and protein levels throughout the degenerative phase and the reinnervation process and evaluated the associated cholinergic sprouting following ECL in the adult mouse brain.

Function and comorbidities of apolipoprotein e in Alzheimer's disease.

Alzheimer's disease (AD)-the most common type of dementia among the elderly-represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE), the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk.

Inhibition of cortical astrocyte differentiation by Hes6 requires amino- and carboxy-terminal motifs important for dimerization and phosphorylation.

Hairy/Enhancer of split (Hes) 6 is a basic helix-loop-helix protein that interacts with the transcriptional co-repressor, Groucho, and antagonizes the neural functions of the Notch pathway. More specifically, mouse Hes6 regulates cerebral corticogenesis by promoting neurogenesis and suppressing astrocyte differentiation. The molecular mechanisms underlying the anti-astrogenic function of Hes6 are poorly defined.

Hes6 inhibits astrocyte differentiation and promotes neurogenesis through different mechanisms.

The mechanisms regulating the generation of cell diversity in the mammalian cerebral cortex are beginning to be elucidated. In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neurons. In contrast, a related Hes family member termed Hes6 promotes neurogenesis.

Antagonistic effects of Grg6 and Groucho/TLE on the transcription repression activity of brain factor 1/FoxG1 and cortical neuron differentiation.

Groucho (Gro)/TLE transcriptional corepressors are involved in a variety of developmental mechanisms, including neuronal differentiation. They contain a conserved C-terminal WD40 repeat domain that mediates interactions with several DNA-binding proteins. In particular, Gro/TLE1 interacts with forkhead transcription factor brain factor 1 (BF-1; also termed FoxG1).

Hes6 promotes cortical neurogenesis and inhibits Hes1 transcription repression activity by multiple mechanisms.

Hes1 is a mammalian basic helix-loop-helix transcriptional repressor that inhibits neuronal differentiation together with corepressors of the Groucho (Gro)/Transducin-like Enhancer of split (TLE) family. The interaction of Hes1 with Gro/TLE is mediated by a WRPW tetrapeptide present in all Hairy/Enhancer of split (Hes) family members. In contrast to Hes1, the related protein Hes6 promotes neuronal differentiation.

The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.

Seven secretory mammalian kexin-like subtilases have been identified that cleave a variety of precursor proteins at monobasic and dibasic residues. The recently characterized pyrolysin-like subtilase SKI-1 cleaves proproteins at nonbasic residues. In this work we describe the properties of a proteinase K-like subtilase, neural apoptosis-regulated convertase 1 (NARC-1), representing the ninth member of the secretory subtilase family.