A promising connection between BDNF and Alzheimer’s disease

Giuffrida, Maria Laura; Copani, Agata; Rizzarelli, Enrico

doi:10.18632/aging.101518

Cited by 47 publications

(34 citation statements)

References 7 publications

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“…11). Interestingly, TNF, whose transcription was not altered upon knockdown of Arc, regulates 15 genes (Table 7), the top five of which are Casp8 (neuroinflammation) 97 , Ptgs2 (also regulated by APP and CREB1), Gabrg2 (neuroinflammation) 98,99 , Bdnf (synaptogenesis; neuroinflammation, AD progression) [100][101][102][103] and Penk (opioid signaling, AD progression) 104 . While the top CREB1-regulated genes are mainly associated with the opioid signaling pathway, APP and TNF are implicated in neuroinflammation.…”

Section: Upstream Regulators Associated With Arc-dependent Genesmentioning

confidence: 99%

Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Leung

Gwq

VanDongen

2019

Preprint

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The immediate-early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Arc protein is localized to excitatory synapses, where it controls AMPA receptor endocytosis, and to the nucleus, where it associates with Tip60, a subunit of a chromatin modifying complex. Here we show that Arc interacts with dynamic chromatin loops and associates with histone markers for active enhancers and transcription in cultured hippocampal neurons. When Arc induction by pharmacological network activation was prevented using a short hairpin RNA, the expression profile was altered for over 1900 genes. Many gene families were affected by the absence of Arc, most notably those associated with synaptic function, neuronal plasticity, intrinsic excitability (channels, receptors, transporters), and signaling pathways (transcription factors/regulators). Interestingly, about 100 genes whose activitydependent expression level depends on Arc are associated with the pathophysiology of Alzheimer's disease, suggesting a critical role for Arc in the development of neurodegenerative disorders. When endogenous Arc expression was induced in a non-neuronal cell line (HEK293T), the transcription of many neuronal genes was increased, suggesting Arc can control expression in the absence of activated signaling pathways. Taken together, these data establish Arc as a master regulator of neuronal activity-dependent gene expression and a significant factor underlying the pathophysiology Alzheimer's disease.

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Section: Upstream Regulators Associated With Arc-dependent Genesmentioning

confidence: 99%

Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Leung

Gwq

VanDongen

2019

Preprint

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“…According to the research of Wei et al, it is shown that pratensein can promote the expression of NEP and reduce the deposition of Aβ [50]. In addition, early studies have shown that during the occurrence and development of AD, the expression of BDNF is reduced both in mRNA and protein levels [51][52][53]. Increased BDNF in the blood slowed AD development and cognitive decline [51,[53][54][55].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, early studies have shown that during the occurrence and development of AD, the expression of BDNF is reduced both in mRNA and protein levels [51][52][53]. Increased BDNF in the blood slowed AD development and cognitive decline [51,[53][54][55]. Studies have shown that the expression of BDNF is significantly reduced in an Aβ 1-42 -induced rat model, while pratensein can reverse the decrease of BDNF expression [50].…”

Section: Discussionmentioning

confidence: 99%

Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro

Sun

Yuan

et al. 2020

Mediators of Inflammation

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Alzheimer’s disease (AD) is a common neurodegenerative disease. Aβ plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aβ toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aβ-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aβ-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.

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“…Meanwhile, it has become obvious that Aβ peptides derived from amyloid precursor protein have dramatic effects on synaptic transmission in the pathogenesis of neurodegenerative diseases. Because neurotrophins and Aβ are used for affecting both synaptic and cognitive function, it is probable that their mechanisms of action might even intersect (Giuffrida, Copani, & Rizzarelli, ).…”

Section: Discussionmentioning

confidence: 99%

Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain‐derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element‐binding signaling pathway

Yan

et al. 2019

Phytotherapy Research

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Kaempferide (KF) is a compound of flavonoids from Alpinae oxyphylla Miq, and the herb itself is used as a classical tonic agent. This paper aims to investigate the effects of KF on cognitive function impairment and neurodegeneration in the mouse model of Alzheimer's disease induced by intracerebroventricular (ICV) injection of Aβ 1-42 . The mice were treated with KF at doses of 0.02 and 0.2 mg/kg/day (ICV) for five consecutive days after Aβ 1-42 exposures. The behavioral test results showed that KF could prevent cognitive decline in mice induced by Aβ 1-42 as assessed by the locomotor activity test, Y-maze test, and Morris water maze test.Furthermore, the activities of superoxide dismutase and malondialdehyde in the hippocampus and cerebral cortex were elevated by KF administration. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with KF. In addition, we found KF could boost brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding (CREB) protein signal in the hippocampus.All results illustrated that KF could exert neuroprotective effects at least partly through alleviating oxidative stress and enhancing the BDNF/TrkB/CREB pathway in Aβ 1-42 -induced mice.

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A promising connection between BDNF and Alzheimer’s disease

Cited by 47 publications

References 7 publications

Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease

Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro

Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain‐derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element‐binding signaling pathway

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