Beneficial Effect of a Selective Adenosine A Receptor Antagonist in the APPswe/PS1dE9 Mouse Model of Alzheimer's Disease.

Consumption of caffeine, a non-selective adenosine A receptor (AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) and mitigates both amyloid and Tau lesions in transgenic mouse models of the disease. While short-term treatment with AR antagonists have been shown to alleviate cognitive deficits in mouse models of amyloidogenesis, impact of a chronic and long-term treatment on the development of amyloid burden, associated neuroinflammation and memory deficits has never been assessed. In the present study, we have evaluated the effect of a 6-month treatment of APPsw/PS1dE9 mice with the potent and selective AR antagonist MSX-3 from 3 to 9-10 months of age.

Toll-like receptors promote inflammation in idiopathic inflammatory myopathies.

The roles of Toll-like receptors (TLRs) and their myeloid differentiation response gene 88 (MyD88)-dependent and MyD88-independent signaling cascade particularly with regard to the pathogenesis and regulation of immune responses in idiopathic inflammatory myopathies are unclear. We investigated these pathways in muscle biopsies from 5 cases each of polymyositis, inclusion body myositis, dermatomyositis, vasculitis-associated interstitial myositis, and noninflammatory neurogenic atrophy. Toll-like receptor 2, TLR4, TLR9, and MyD88 mRNA transcripts and protein expression were increased in all subtypes of idiopathic inflammatory myopathies.