The roles of amyloid precursor protein (APP) in neurogenesis

Zhou, Zhidong; Chan, Christine Hui-shan; Ma, Quanhong; Xu, Xianglan; Xiao, Zhicheng; Tan, Eng‐King

doi:10.4161/cam.5.4.16986

Cited by 125 publications

(54 citation statements)

References 130 publications

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“…Overexpression of APP and BACE1 contribute to the formation of Aβ and participate in the aging process [17,18,31,32,33]. In this study, we found that the protein level of APP was elevated in both the forebrain cortex and hippocampus of the middle-aged rats compared to young rats (Fig.…”

Section: Resultssupporting

confidence: 56%

Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat

Che

Sun

Guo

et al. 2014

Cell Physiol Biochem

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Background: Aging is associated with the gradual cognitive decline and shows the typical senile plaque formation in the brain, which results from the aggregation of beta amyloid (Aβ) peptide following the abnormal proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. Accumulating evidence indicates that several microRNAs (miRNAs) are involved in the Alzheimer's disease (AD) by regulating the expression of APP and BACE1 proteins. However, the cognitive ability and the expression profile of the APP- and BACE1-associated miRNAs in the middle-aged population are largely unknown. Methods: The learning and memory ability in rats were determined by Morris Water Maze test. The protein levels of APP and BACE1 were detected by western blotting. The quantitative polymerase chain reaction was used to identify the miRNAs levels in forebrain cortex and the hippocampus. Results: Middle-aged rats have declined learning ability without changes in the memory ability, and increased APP and BACE1 protein expression in the forebrain cortex. Computational analysis using Targetscan and Pictar databases reveals that totally 4 predicted miRNAs have conserved binding site with APP, namely miR-106b, -17-5p, -153, -101. All of them showed decreased expression in both the forebrain cortex and hippocampus. Among the 10 predicted miRNAs targeting BACE1, different expression profiles were identified in the forebrain cortex (decreased: miR-9, -19a, -135a, -15b, -16, -195, -29c, -214; increased: miR-124; no change: miR-141) and the hippocampus (decreased: miR-9, -15b, -16, -195, -29c, -124; increased: miR-19a, -135a, -214, -141) in the middle-aged rats compared with the young rats. Conclusion: Our results provided the first evidence that middle-aged rats have begun displaying cognitive disability with abnormal expression of APP- and BACE1-related miRNAs in the hippocampus and forebrain cortex.

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Section: Resultssupporting

confidence: 56%

Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat

Che

Sun

Guo

et al. 2014

Cell Physiol Biochem

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“…Although the exact pathogenesis of AD remains elusive, neurotoxicity of amyloid β peptide (Aβ) is considered a major factor in AD pathogenesis (Rajasekhar et al, 2015) and is closely related to impairment of neurogenesis in the AD brain (Zhou et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

Deep Brain Magnetic Stimulation Promotes Neurogenesis and Restores Cholinergic Activity in a Transgenic Mouse Model of Alzheimer’s Disease

Zhen

Qian

et al. 2017

Front. Neural Circuits

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Alzheimer’s disease (AD) is characterized by progressive decline of memory and cognitive functions. Deep magnetic stimulation (DMS), a noninvasive and nonpharmacological brain stimulation, has been reported to alleviate stress-related cognitive impairment in neuropsychiatric disorders. Our previous study also discovered the preventive effect of DMS on cognitive decline in an AD mouse model. However, the underlying mechanism must be explored further. In this study, we investigated the effect of DMS on spatial learning and memory functions, neurogenesis in the dentate gyrus (DG), as well as expression and activity of the cholinergic system in a transgenic mouse model of AD (5XFAD). Administration of DMS effectively improved performance in spatial learning and memory of 5XFAD mice. Furthermore, neurogenesis in the hippocampal DG of DMS-treated 5XFAD mice was clearly enhanced. In addition, DMS significantly raised the level of acetylcholine and prevented the increase in acetylcholinesterase activity as well as the decrease in acetyltransferase activity in the hippocampus of 5XFAD mice. These findings indicate that DMS may be a promising noninvasive tool for treatment and prevention of AD cognitive impairment by promoting neurogenesis and enhancing cholinergic system function.

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“…In the trophic factor deprivation paradigm, APP cleavage by Beta-site APP cleavage enzyme (BACE1) activates caspase-6 and caspase-3 pathways in axons and neuronal cell body, respectively (Vohra et al 2010, Nikolaev et al 2009). The accumulation of Aβ causes neuronal damage in Alzheimer’s disease (O’Brein & Wong 2011, Zhou et al 2011) and Aβ also contributes to the formation of intracellular neurofibrillary tangles, which further accelerates the process of neuronal loss and causes the symptoms of dementia (Takata & Kitamura 2012). …”

Section: Introductionmentioning

confidence: 99%

Axon degeneration is key component of neuronal death in amyloid-β toxicity

Alobuia

Wei

Vohra

2013

Neurochemistry International

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Depending upon the stimulus, neuronal cell death can either be triggered from the cell body (soma) or the axon. We investigated the origin of the degeneration signal in amyloid β (Aβ) induced neuronal cell death in cultured in vitro hippocampal neurons. We discovered that Aβ1–42 toxicity-induced axon degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl inhibited both axonal and cell body degeneration in the Aβ-42 treated neurons. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) blocks axon degeneration in a variety of paradigms, but it cannot block neuronal cell body death. Therefore, if the neuronal death signals in Aβ1–42 toxicity originate from degenerating axons, we should be able to block neuronal death by inhibiting axon degeneration. To explore this possibility we over-expressed Nmnat1 in hippocampal neurons. We found that inhibition of axon degeneration in Aβ1–42 treated neurons prevented neuronal cell death. Thus, we conclude that axon degeneration is the key component of Aβ1–42 induced neuronal degeneration, and therapies targeting axonal protection can be important in finding a treatment for Alzheimer’s disease.

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The roles of amyloid precursor protein (APP) in neurogenesis

Cited by 125 publications

References 130 publications

Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat

Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat

Deep Brain Magnetic Stimulation Promotes Neurogenesis and Restores Cholinergic Activity in a Transgenic Mouse Model of Alzheimer’s Disease

Axon degeneration is key component of neuronal death in amyloid-β toxicity

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