Metabolic stringent response in intracellular stages of Leishmania.

Leishmania are unusual in being able to survive long-term in the mature phagolysosome compartment of macrophages and other phagocytic cells in their mammalian hosts. Key to their survival in this niche, Leishmania amastigotes switch to a slow growth state and activate a stringent metabolic response. The stringent metabolic response may be triggered by multiple stresses and is associated with decreased metabolic fluxes, restricted use of sugars and fatty acids as carbon sources and increased dependence on metabolic homeostasis pathways.

Inhibition of gamma-secretase as a therapeutic intervention for Alzheimer's disease: prospects, limitations and strategies.

Genetic and experimental evidence points to amyloid-beta (Abeta) peptide as the culprit in Alzheimer's disease pathogenesis. This protein fragment abnormally accumulates in the brain cortex and hippocampus of patients with Alzheimer's disease, and self-aggregates to form toxic oligomers causing neurodegeneration.Abeta is heterogeneous and produced from a precursor protein (amyloid precursor protein [APP]) by two sequential proteolytic cleavages that involve beta- and gamma-secretases.