Role of GPCR signaling and calcium dysregulation in Alzheimer's disease

Alzheimer's disease (AD), a late onset neurodegenerative disorder is characterized by the loss of memory, disordered cognitive function, caused by accumulation of amyloid-β (Aβ) peptide and neurofibrillary tangles (NFTs) in the neocortex and hippocampal brain area. Extensive research has been done on the findings of the disease etiology or pathological causes of aggregation of Aβ and hyperphosphorylation of tau protein without much promising results. Recently, calcium dysregulation has been reported to play an important role in the pathophysiology of AD. Calcium ion acts as one of the major secondary messengers, regulates many signaling pathways involved in cell survival, proliferation, differentiation, transcription and apoptosis. Calcium signaling is one of the major signaling pathways involved in the formation of memory, generation of energy and other physiological functions. It also can modulate function of many proteins upon binding. Dysregulation in calcium homeostasis leads to many physiological changes leading to neurodegenerative diseases including AD. In AD, GPCRs generate secondary messengers which regulate calcium homeostasis inside the cell and is reported to be disturbed in the pathological condition. Calcium channels and receptors present on the plasma membrane and intracellular organelle maintain calcium homeostasis through different signaling mechanisms. In this review, we have summarized the different calcium channels and receptors involved in calcium dysregulation which in turn play a critical role in the pathogenesis of AD. Understanding the role of calcium channels and GPCRs to maintain calcium homeostasis is an attempt to develop effective AD treatments.