MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases

Catanesi, Mariano; d’Angelo, Michele; Tupone, Maria Grazia; Benedetti, Elisabetta; Giordano, Antonio; Castelli, Vanessa; Cimini, Annamaria

doi:10.3390/ijms21175986

Cited by 76 publications

(59 citation statements)

References 170 publications

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“…Excessive oxidative stress induces mitochondrial impairment and causes a decrease in ATP production, altered calcium homeostasis and a further increase in reactive oxygen species production. These events lead to DNA, lipid and protein damage and long-term increase can cause mitochondrial DNA mutation, ultimately progressing the disease severity [46] Moreover, this oxidative stress may aggravate a vicious and interminable cycle of neuro-inflammation, which further promotes oxidative stress [47,48]. Previous studies also substantiate ICV-STZ-induced decreased GSH and increased MDA levels in the cortex and hippocampus [8].…”

Section: Discussionmentioning

confidence: 85%

Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer’s Disease in Rats

Verma

Singh

2020

Brain Sciences

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The role of oxidative stress, neuro-inflammation and cholinergic dysfunction is already established in the development of Alzheimer’s disease (AD). Sinapic acid (SA), a hydroxylcinnamic acid derivative, has shown neuro-protective effects. The current study evaluates the neuro-protective potential of SA in intracerebroventricular streptozotocin (ICV-STZ) induced cognitive impairment in rats. Male Wistar rats were bilaterally injected with ICV-STZ. SA was administered intragastrically once daily for three weeks. Rats were divided into sham, ICV-STZ, STZ + SA (10 mg/kg), STZ + SA (20 mg/kg) and SA per se (20 mg/kg). Behavioral tests were assessed on day 0 and 21 days after STZ. Later, rats were sacrificed for biochemical parameters, pro-inflammatory cytokines, choline acetyltransferase (ChAT) expression and neuronal loss in the CA1 region of the hippocampus. The results showed that SA 20 mg/kg significantly (p < 0.05) improved cognitive impairment as assessed by Morris water maze and passive avoidance tests. SA 20 mg/kg reinstated the altered levels of GSH, MDA, TNF-α and IL-1β in the cortex and hippocampus. STZ-induced decreased expression of ChAT and neuronal loss were also significantly (p < 0.05) improved with SA. Our results showed that SA exhibits neuro-protection against ICV-STZ induced oxidative stress, neuro-inflammation, cholinergic dysfunction and neuronal loss, suggesting its potential in improving learning and memory in patients of AD.

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Section: Discussionmentioning

confidence: 85%

Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer’s Disease in Rats

Verma

Singh

2020

Brain Sciences

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“…Aβ-induced cytotoxicity is linked to oxidative stress [ 11 , 12 ], perturbation of intracellular calcium homeostasis [ 13 ], overproduction of tumor necrosis factor-α (TNF-α) [ 14 ], mitochondrial dysfunction [ 11 , 12 , 15 ] and apoptosis [ 10 , 16 , 17 ]. Determining the underlying mechanism of neuronal cell death induced by Aβ is an essential step in treating AD.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of Vitamin K2 Protection against Amyloid-β-Induced Cytotoxicity

2021

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The pathological role of vitamin K2 in Alzheimer’s disease (AD) involves a definite link between impaired cognitive functions and decreased serum vitamin K levels. Vitamin K2 supplementation may have a protective effect on AD. However, the mechanism underlying vitamin K2 protection has not been elucidated. With the amyloid-β (Aβ) cascade hypothesis, we constructed a clone containing the C-terminal fragment of amyloid precursor protein (β-CTF/APP), transfected in astroglioma C6 cells and used this cell model (β-CTF/C6) to study the protective effect of vitamin K2 against Aβ cytotoxicity. Both cellular and biochemical assays, including cell viability and reactive oxygen species (ROS), assays assay, and Western blot and caspase activity analyses, were used to characterize and unveil the protective role and mechanism of vitamin K2 protecting against Aβ-induced cytotoxicity. Vitamin K2 treatment dose-dependently decreased the death of neural cells. The protective effect of vitamin K2 could be abolished by adding warfarin, a vitamin K2 antagonist. The addition of vitamin K2 reduced the ROS formation and inhibited the caspase-3 mediated apoptosis induced by Aβ peptides, indicating that the mechanism underlying the vitamin K2 protection is likely against Aβ-mediated apoptosis. Inhibitor assay and Western blot analyses revealed that the possible mechanism of vitamin K2 protection against Aβ-mediated apoptosis might be via regulating phosphatidylinositol 3-kinase (PI3K) associated-signaling pathway and inhibiting caspase-3-mediated apoptosis. Our study demonstrates that vitamin K2 can protect neural cells against Aβ toxicity.

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“…In contrast, Catanesi et al (2020) reported that miR-98 endorses Aβ formation by targeting insulinlike growth factor 1 implying its pathological role in AD. miR-15a, miR-34a, miR-126, miR-181a, miR-210-3p, miR-425, and miR-424 remained upregulated in AD, which can endorse structural and functional loss of mitochondria and found to play pathological roles in AD (Catanesi et al, 2020;John et al, 2020). miR-27a and miR-101 negatively regulate mitophagy, which remains upregulated in AD (John TA B L E 1 Role of different types of miRs on mitochondrial dynamic proteins miRNAs Functions miR-499 Suppression of calcineurin-mediated dephosphorylation of Drp1 (Wang et al, 2011) miR-140 Promotes mitochondrial fission and Apoptosis by downregulating Mfn1 miR-761 Downregulation of Mitochondrial Fission Factor (MFF) (Long et al, 2013) miR-34b/c Downregulation of miR-34b/c leads to reduced expression of DJ1 and Parkin-promoting mitochondrial fragmentation in Parkinson's disease (Minones-Moyano et al, 2011).…”

Section: Role Of Mirs In Mitochondrial Biogenesis Dynamics and MImentioning

confidence: 95%

“…miR-98 can mitigate mitochondrial dysfunctions and reduce Aβ formation through preventing Notch pathway via targeting hairy and enhancer of split (Hes)-related with YRPW motif protein 2 (HEY2) (Amakiri et al, 2019). In contrast, Catanesi et al (2020) reported that miR-98 endorses Aβ formation by targeting insulinlike growth factor 1 implying its pathological role in AD. miR-15a, miR-34a, miR-126, miR-181a, miR-210-3p, miR-425, and miR-424 remained upregulated in AD, which can endorse structural and functional loss of mitochondria and found to play pathological roles in AD (Catanesi et al, 2020;John et al, 2020).…”

Section: Role Of Mirs In Mitochondrial Biogenesis Dynamics and MImentioning

confidence: 99%

“…(2020) reported that miR‐98 endorses Aβ formation by targeting insulin‐like growth factor 1 implying its pathological role in AD. miR‐15a, miR‐34a, miR‐126, miR‐181a, miR‐210‐3p, miR‐425, and miR‐424 remained upregulated in AD, which can endorse structural and functional loss of mitochondria and found to play pathological roles in AD (Catanesi et al., 2020; John et al., 2020). miR‐27a and miR‐101 negatively regulate mitophagy, which remains upregulated in AD (John et al., 2020).…”

Section: Failure Of the Ubiquitin–proteasome System In Neurodegeneratmentioning

confidence: 99%

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Mitochondrial dysfunction, mitophagy, and role of dynamin‐related protein 1 in Alzheimer's disease

Medala

Gollapelli

Dewanjee

et al. 2021

J of Neuroscience Research

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Alzheimer's disease (AD) is the most common type of dementia and progressive neurodegenerative disease. The presence of β-amyloid (Aβ) plaques and phosphorylated Tau tangles are considered to be the two main hallmarks of AD. Recent findings have shown that different changes in the structure and dynamics of mitochondria play an important role in AD pathology progression. Mitochondrial changes in AD are expressed as enhanced mitochondrial fragmentation, altered mitochondrial dynamics, and changes in the expression of mitochondrial biogenesis genes in vitro and in vivo models. Therefore, targeting mitochondria and associated mitochondrial proteins seems to be a promising alternative instead of targeting Aβ and Tau in the prevention of Alzheimer's disease. The dynamin-related protein (Drp1) is one such protein that plays an important role in the regulation of mitochondrial division and maintenance of mitochondrial structures. Few researchers have shown that inhibition of Drp1 GTPase activity in neuronal cells rescues excessive mitochondrial fragmentation. In addition, the growing evidence revealed that Drp1 can interact with both Aβ and Tau protein in human brain tissues and mouse models. In this review, we would like to update existing knowledge about various changes in and around mitochondria related to the pathogenesis of Alzheimer's disease, with particular emphasis on mitophagy and autophagy. | 1121 MEDALA Et AL.

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MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases

Cited by 76 publications

References 170 publications

Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer’s Disease in Rats

Sinapic Acid Alleviates Oxidative Stress and Neuro-Inflammatory Changes in Sporadic Model of Alzheimer’s Disease in Rats

Molecular Mechanism of Vitamin K2 Protection against Amyloid-β-Induced Cytotoxicity

Mitochondrial dysfunction, mitophagy, and role of dynamin‐related protein 1 in Alzheimer's disease

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