Early calcium dysregulation in Alzheimer's disease:setting the stage for synaptic dysfunction  

作　　者：Shreaya CHAKROBORTY Grace E.STUTZMANN 

机构地区：[1]Department of Neuroscience,Rosalind Franklin University/the Chicago Medical School

出　　处：《Science China(Life Sciences)》2011年第8期752-762,共11页中国科学（生命科学英文版）

摘　　要：Alzheimer's disease(AD) is an irreversible and progressive neurodegenerative disorder with no known cure or clear understanding of the mechanisms involved in the disease process.Amyloid plaques,neurofibrillary tangles and neuronal loss,though characteristic of AD,are late stage markers whose impact on the most devastating aspect of AD,namely memory loss and cognitive deficits,are still unclear.Recent studies demonstrate that structural and functional breakdown of synapses may be the underlying factor in AD-linked cognitive decline.One common element that presents with several features of AD is disrupted neuronal calcium signaling.Increased intracellular calcium levels are functionally linked to presenilin mutations,ApoE4 expression,amyloid plaques,tau tangles and synaptic dysfunction.In this review,we discuss the role of AD-linked calcium signaling alterations in neurons and how this may be linked to synaptic dysfunctions at both early and late stages of the disease.Alzheimer＇s disease（AD） is an irreversible and progressive neurodegenerative disorder with no known cure or clear understanding of the mechanisms involved in the disease process.Amyloid plaques,neurofibrillary tangles and neuronal loss,though characteristic of AD,are late stage markers whose impact on the most devastating aspect of AD,namely memory loss and cognitive deficits,are still unclear.Recent studies demonstrate that structural and functional breakdown of synapses may be the underlying factor in AD-linked cognitive decline.One common element that presents with several features of AD is disrupted neuronal calcium signaling.Increased intracellular calcium levels are functionally linked to presenilin mutations,ApoE4 expression,amyloid plaques,tau tangles and synaptic dysfunction.In this review,we discuss the role of AD-linked calcium signaling alterations in neurons and how this may be linked to synaptic dysfunctions at both early and late stages of the disease.

关 键 词：CALCIUM Alzheimer＇s NEURON synaptic dysfunction plasticity ER RYANODINE CICR 

分 类 号：R749.16[医药卫生—神经病学与精神病学]