Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • ML-7 hydrochloride Blood serum and plasma contain a range of

    2020-08-05

    Blood serum and plasma contain a range of enzymes that could potentially catalyze the hydrolysis of urea derivatives. Therefore it is possible for the prodrugs to be prematurely hydrolyzed by the plasma enzymes leading to the release of triazenes before reaching the pre-localized CPG2. Consequently, we were interested in examining the stability of prodrugs in human plasma. Experimental procedure is detailed in .
    Introduction Alzheimer\'s disease (AD) is an irreversible neurodegenerative disease that is the most common cause of dementia and that is clinically characterized by progressive loss of the ability of learning and memory. In 2015, approximately 46.8 million people were diagnosed with AD in the world and this number is expected to increase to 131.5 million by 2050 (Prince et al., 2015). AD is histopathologically characterized by extracellular amyloid plaques that are primarily composed of amyloid beta (Aβ) peptides and intercellular neurofibrillary tangles, which result from accumulation of the hyper-phosphorylated microtubule-associated protein tau (Castellani et al., 2010). Previous reports indicated that extracellular deposits of Aβ peptides are the principal cause of AD onset (Hardy and Higgins, 1992, Tanzi, 2005, De Strooper, 2010) and that the innate immune function of microglia could prevent Aβ accumulation (Wang et al., 2015). It was recently reported that a functional single nucleotide polymorphism (rs75932628) within Triggering receptor expressed on myeloid ML-7 hydrochloride 2 (TREM2) is associated with AD (Guerreiro et al., 2013). Homozygous loss of function mutations in TREM2 are also associated with an autosomal recessive form of early onset dementia, presenting with bone cysts and consequent fractures called polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, or Nasu-Hakola disease (Paloneva et al., 2003). TREM2 activates the innate immune response in macrophages and dendritic cells (N\'Diaye et al., 2009). In the brain, TREM2 is expressed in microglia and promotes phagocytosis of apoptotic neurons, cellular debris, and misfolded proteins by the recognition of specific endogenous ligands on the surface of apoptotic cells (Jonsson and Stefansson, 2013). Subsequently, TREM2 delays the inflammatory response by suppressing microglial cytokine production (Hsieh et al., 2009). TREM2 deficiency augmented Aβ accumulation and neuronal loss in a mouse model of AD (Wang et al., 2015). In addition, higher TREM2 mRNA expression was predominantly associated with the increase of phosphorylated tau in AD patient brains (Lue et al., ML-7 hydrochloride 2015). Recently, peripheral leukocytes were reported to be indicated in AD pathogenesis (Zenaro et al., 2015). Gene expression and DNA methylation changes in leukocytes have been observed in neuropsychiatric conditions including AD (Yamazaki et al., 2016, Yoshino et al., 2016a, Yoshino et al., 2016b, Yoshino et al., 2016c, Funahashi et al., 2016). DNA methylation, a type of epigenetic modification, plays a key role in regulating gene expression (Abdolmaleky et al., 2004). Although we reported higher TREM2 mRNA expression in the leukocytes of AD subjects (Mori et al., 2015), methylation rates of TREM2 have not yet been examined.