scholarly journals Composite mathematical modeling of calcium signaling behind neuronal cell death in Alzheimer’s disease

2018 ◽  
Vol 12 (S1) ◽  
Author(s):  
Bobby Ranjan ◽  
Ket Hing Chong ◽  
Jie Zheng
Keyword(s):  
Mathematical Modeling ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Calcium Signaling ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and increases neuronal cell death

2014 ◽  
Vol 20 (12) ◽  
pp. 1452-1457 ◽  
Author(s):  
Monica K Wetzel-Smith ◽  
◽  
Julie Hunkapiller ◽  
Tushar R Bhangale ◽  
Karpagam Srinivasan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Late Onset ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rare Mutation

Interactions between BIM Protein and Beta-Amyloid May Reveal a Crucial Missing Link between Alzheimer’s Disease and Neuronal Cell Death

2019 ◽  
Vol 10 (8) ◽  
pp. 3555-3564 ◽  
Author(s):  
Ravit Malishev ◽  
Sukhendu Nandi ◽  
Dariusz Śmiłowicz ◽  
Shamchal Bakavayev ◽  
Stanislav Engel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Beta Amyloid ◽  
Missing Link

scholarly journals Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer’s disease pathologies

2019 ◽  
Vol 116 (18) ◽  
pp. 9094-9102 ◽  
Author(s):  
Jie Xiang ◽  
Zhi-Hao Wang ◽  
Eun Hee Ahn ◽  
Xia Liu ◽  
Shan-Ping Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Trophic Factor ◽  
Tau Pathology ◽  
Trkb Receptors ◽  
Repeat Domain

BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer’s disease (AD). BDNF deficiency’s association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Here we show that BDNF deprivation triggers Tau proteolytic cleavage by activating δ-secretase [i.e., asparagine endopeptidase (AEP)], and the resultant Tau N368 fragment binds TrkB receptors and blocks its neurotrophic signals, inducing neuronal cell death. Knockout of BDNF or TrkB receptors provokes δ-secretase activation via reducing T322 phosphorylation by Akt and subsequent Tau N368 cleavage, inducing AD-like pathology and cognitive dysfunction, which can be restored by expression of uncleavable Tau N255A/N368A mutant. Blocking the Tau N368–TrkB complex using Tau repeat-domain 1 peptide reverses this pathology. Thus, our findings support that BDNF reduction mediates Tau pathology via activating δ-secretase in AD.

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