Magnesium modulates amyloid-β protein precursor trafficking and processing.

摘要: Alzheimer's disease (AD), the most common form of dementia, is characterized by presence excessive deposits aggregated amyloid-beta (Abeta), which derived from protein precursor (AbetaPP) following processing beta- and gamma-secretase. Metal elements are implicated in pathophysiology AD. Magnesium affects many biochemical mechanisms vital for neuronal properties synaptic plasticity, magnesium levels were reported to be decreased various tissues including brain AD patients. However, exact role neurodegenerative process remains elusive. In this study, we investigated effects physiological (0.8 mM, as normal control), low (0-0.4 mM), high (1.2-4.0 mM) concentrations extracellular ([Mg2+]o) on AbetaPP Abeta secretion. Here show varying [Mg2+]o time- dose-dependent. After 24 h treatment, increased C-terminal fragment-alpha (CTFalpha) soluble alpha-secretase cleaved (sAbetaPPalpha) release via enhancing retention plasma membrane. contrast, enhanced CTFbeta accumulation secretion, reduced cell surface level. Varying did not alter contents full length AbetaPP. total intracellular level deprivation over hr impaired viability. Normal could restored when was adjusted back concentration. These data demonstrate that can modulated at [Mg2+]o, favors cleavage pathway. Our findings suggest supplementation has a therapeutic potential preventing