Commentary Cellscience Reviews Vol 5 No 1 ISSN 1742-8130

Oligomeric amyloid beta peptide alters phosphatidylinositol-4, 5-bisphosphate metabolism in neurons

Amyloid beta peptide (Aβ) has been implicated as a key factor underlying the ‘synaptic failure’ hypothesis in Alzheimer’s disease (AD). Recent studies have focused upon our understanding of the molecular mechanism(s) through which the oligomeric form of Aβ (oAβ) impairs the neuronal excitatory processes leading to memory deficit. There is evidence that Aβ targets the N-methyl-D-aspartic acid (NMDA) receptor and subsequently alters its downstream signaling pathways, leading to an increased production of reactive oxygen species (ROS), mitochondrial dysfunction, altered synaptic vesicle recycling, cytoskeletal rearrangement, and enhanced apoptotic cell death. The study by Berman et al., (2008) provides a new molecular association between oAβ and phosphatidylinositol-4,5-bisphosphate (PIP2) in neurons through the activation of phospholipase Cδ (PLCδ). This study also suggests that synaptojanin 1, a PtdIns(4,5)P2 phosphatase, is a major regulator of PIP2 turnover and synaptic homeostasis.

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