TY - JOUR
T1 - Rectifying attenuated store-operated calcium entry as a therapeutic approach for alzheimer’s disease
AU - Huang, Alexis S.
AU - Tong, Benjamin C.K.
AU - Wu, Aston J.
AU - Chen, Xiaotong
AU - Sreenivasmurthy, Sravan G.
AU - Zhu, Zhou
AU - Liu, Jia
AU - Su, Chengfu
AU - Li, Min
AU - Cheung, King Ho
N1 - Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Although the pathological hallmarks of AD have been identified, the derived therapies cannot effectively slow down or stop disease progression; hence, it is likely that other pathogenic mechanisms are involved in AD pathogenesis. Intracellular calcium (Ca2+) dyshomeostasis has been consistently observed in AD patients and numerous AD models and may emerge prior to the development of amyloid plaques and neurofibrillary tangles. Thus, intracellular Ca2+ disruptions are believed to play an important role in AD development and could serve as promising therapeutic intervention targets. One of the disrupted intracellular Ca2+ signaling pathways manifested in AD is attenuated store-operated Ca2+ entry (SOCE). SOCE is an extracellular Ca2+ entry mechanism mainly triggered by intracellular Ca2+ store depletion. Maintaining normal SOCE function not only provides a means for the cell to replenish ER Ca2+ stores but also serves as a cellular signal that maintains normal neuronal func-tions, including excitability, neurogenesis, neurotransmission, synaptic plasticity, and gene expression. However, normal SOCE function is diminished in AD, resulting in disrupted neuronal spine stability and synaptic plasticity and the promotion of amyloidogenesis. Mounting evidence suggests that rectifying diminished SOCE in neurons may intervene with the progression of AD. In this review, the mechanisms of SOCE disruption and the associated pathogenic impacts on AD will be discussed. We will also highlight the potential therapeutic targets or approaches that may help ameliorate SOCE deficits for AD treatment.
AB - Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Although the pathological hallmarks of AD have been identified, the derived therapies cannot effectively slow down or stop disease progression; hence, it is likely that other pathogenic mechanisms are involved in AD pathogenesis. Intracellular calcium (Ca2+) dyshomeostasis has been consistently observed in AD patients and numerous AD models and may emerge prior to the development of amyloid plaques and neurofibrillary tangles. Thus, intracellular Ca2+ disruptions are believed to play an important role in AD development and could serve as promising therapeutic intervention targets. One of the disrupted intracellular Ca2+ signaling pathways manifested in AD is attenuated store-operated Ca2+ entry (SOCE). SOCE is an extracellular Ca2+ entry mechanism mainly triggered by intracellular Ca2+ store depletion. Maintaining normal SOCE function not only provides a means for the cell to replenish ER Ca2+ stores but also serves as a cellular signal that maintains normal neuronal func-tions, including excitability, neurogenesis, neurotransmission, synaptic plasticity, and gene expression. However, normal SOCE function is diminished in AD, resulting in disrupted neuronal spine stability and synaptic plasticity and the promotion of amyloidogenesis. Mounting evidence suggests that rectifying diminished SOCE in neurons may intervene with the progression of AD. In this review, the mechanisms of SOCE disruption and the associated pathogenic impacts on AD will be discussed. We will also highlight the potential therapeutic targets or approaches that may help ameliorate SOCE deficits for AD treatment.
KW - Alzheimer’s disease
KW - Calcium signaling
KW - Neurodegenerative disor-der
KW - Neurotransmission
KW - Store-operated calcium entry
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U2 - 10.2174/1567205018666210119150613
DO - 10.2174/1567205018666210119150613
M3 - Article
C2 - 33463469
AN - SCOPUS:85100066981
SN - 1567-2050
VL - 17
SP - 1071
EP - 1087
JO - Current Alzheimer Research
JF - Current Alzheimer Research
IS - 12
ER -