Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam in a human neuronal cell model of early Alzheimer's disease

Mutations in the BRI gene are thought to cause dementias in members of families. The clinical symptoms are similar to those of Alzheimer's disease, but with additional ocular and hearing deficits, and spasticity. The mutations lead to the release of the 34-residue peptides, ABri and ADan, in the brains of afflicted individuals. We have synthesized the peptides in their straight-chain and oxidized cyclic forms and shown that the oxidized form of ABri and reduced form of ADan are toxic to human neuronal cell lines in culture. Neurotoxicity correlates with the extent of formation of SDS-stable non-fibrillar low-molecular-mass oligomers (SSNFOs).

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A Human Stem Cell Model of Early Alzheimer's Disease Pathology in Down Syndrome

Science Translational Medicine ◽

10.1126/scitranslmed.3003771 ◽

2012 ◽

Vol 4 (124) ◽

pp. 124ra29-124ra29 ◽

Cited By ~ 147

Author(s):

Y. Shi ◽

P. Kirwan ◽

J. Smith ◽

G. MacLean ◽

S. H. Orkin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Down Syndrome ◽

Stem Cell ◽

Cell Model ◽

Human Stem Cell ◽

Stem Cell Model ◽

Early Alzheimer’S Disease

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The Mechanism of Catalpol in Alzheimer’s Disease by Modulating Mitochondrial Function Through miR-124-Mediated STIM2

10.21203/rs.3.rs-526939/v1 ◽

2021 ◽

Author(s):

Xin Lv ◽

Jun Qiu ◽

Tao Hao ◽

Haoran Zhang ◽

Haiping Jiang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mitochondrial Function ◽

Hippocampal Neurons ◽

Memory Impairment ◽

Cell Model ◽

Mitochondrial Damage ◽

Ros Generation ◽

Oxygen Species

Abstract Alzheimer’s disease (AD) is a dementia-related disease with cognitive deterioration and memory impairment. Catalpol was reported to relieve impairments in learning and memory. The present study assessed the functional mechanism of catalpol in AD via miR-124/STIM2-mediated mitochondrial function. Primary hippocampal neurons were isolated and cultured. AD cell model was induced by Aβ1−42 and treated with catalpol. APP/PS1 mouse model was established and treated with catalpol and miR-124 agomir. Aβ1−42 induced mitochondrial damage and reactive oxygen species (ROS) generation in AD cell model. Catalpol alleviated mitochondrial damage and reduced ROS generation in hippocampal neurons. miR-124 was highly expressed in AD cell model and catalpol inhibited miR-124 expression. Catalpol alleviated Aβ1−42 induced mitochondrial damage and ROS generation in hippocampal neurons by inhibiting miR-124 expression. miR-124 overexpression after catalpol treatment promoted mitochondrial damage and ROS generation in hippocampal neurons. miR-124 targeted STIM2. Silencing STIM2 after catalpol treatment promoted mitochondrial damage and ROS generation in hippocampal neurons. Catalpol slowed AD progression via the miR-124/STIM2 axis in vivo. The results of the present study indicated that catalpol alleviated mitochondrial damage and ROS generation and thus attenuated AD by regulating miR-124-mediated STIM2.

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