Title:The Phosphoinositide Signal Transduction Pathway in the Pathogenesis of Alzheimer’s Disease
Volume: 15
Issue: 4
关键词:
磷脂酶C，阿尔茨海默病，磷酸肌醇信号传导，预后，诊断，发病机制
摘要: Background: During aging and in age-associated disorders, such as Alzheimer's Disease
(AD), learning abilities decline. Probably, disturbances in signal transduction in brain cells underlie the
cognitive decline. The phosphorylation/dephosphorylation imbalance occurring in degenerating neurons
was recently related to abnormal activity of one or more signal transduction pathways. AD is known to
be associated with altered neuronal Ca2+ homeostasis, as Ca2+ accumulates in affected neurons leading to
functional impairment. It is becoming more and more evident the involvement of signal transduction
pathways acting upon Ca2+ metabolism and phosphorylation regulation of proteins. A growing interest
raised around the role of signal transduction systems in a number of human diseases including neurodegenerative
diseases, with special regard to the systems related to the phosphoinositide (PI) pathway and
AD. The PI signal transduction pathway plays a crucial role, being involved in a variety of cell functions,
such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking,
ion channel activity, cytoskeleton regulation, cell cycle control, apoptosis, cell and tissue polarity,
and contributes to regulate the Ca2+ levels in the nervous tissue.
Conclusion: A number of observations indicated that PI-specific phospholipase C (PLC) enzymes might
be involved in the alteration of neurotransmission. To understand the role and the timing of action of the
signalling pathways recruited during the brain morphology changes during the AD progression might
help to elucidate the aetiopathogenesis of the disease, paving the way to prognosis refinement and/or
novel molecular therapeutic strategies.
