Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading to cell death or neuroprotection

Naoi, M; Maruyama, Wakako; Akao, Yukihiro; Yi, Hong; Yamaoka, Yuriko

doi:10.1007/978-3-211-33328-0_8

Cited by 74 publications

(41 citation statements)

References 47 publications

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“…An increasing number of studies have demonstrated the involvement of MAO in neurodegenerative diseases, including Parkinson's disease (PD) (16,17), AD (18,19), Lewy body diseases with dementia (20) and depression (17,21). MAO is involved in neurodegeneration via oxidative stress, which has a central role in neurodegenerative diseases (22).…”

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

“…MAO is involved in neurodegeneration via oxidative stress, which has a central role in neurodegenerative diseases (22). Other mechanisms have been identified, including neuroinflammation (23), triggering of apoptosis (18,24), failure of aggregated-protein clearance (25)(26)(27) and glial activation (28) by MAO.…”

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

“…In PD, dopaminergic cell death in the substantia nigra is linked to a marked glutathione decrease and mitochondrial dysfunction (24). MAO in the mitochondrial outer membrane induces oxidative stress resulting in neuronal degeneration through the production of hydrogen peroxide by oxidation of monoamine substrates (18,33,34). These results suggest that MAO is involved in the neurodegenerative pathogenesis of PD that manifests as increased oxidative stress and a major impairment of the glutathione pathway.…”

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

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Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Cai

2014

Molecular Medicine Reports

154

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Abstract. Activated monoamine oxidase (MAO) has a critical role in the pathogenesis of Alzheimer's disease (AD), including the formation of amyloid plaques from amyloid β peptide (Aβ) production and accumulation, formation of neurofibrillary tangles, and cognitive impairment via the destruction of cholinergic neurons and disorder of the cholinergic system. Several studies have indicated that MAO inhibitors improve cognitive deficits and reverse Aβ pathology by modulating proteolytic cleavage of amyloid precursor protein and decreasing Aβ protein fragments. Thus, MAO inhibitors may be considered as promising therapeutic agents for AD.

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Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

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Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Cai

2014

Molecular Medicine Reports

154

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“…Furthermore, Bcl-2 overexpression prevented Cyt-c release following peroxynitrite-induced apoptotic signaling, indicating the potential of Bcl-2 as a neuroprotective agent (44). In a previous study, selegiline increased the mRNA and protein levels of Bcl-2 and Bcl-xL in SH-SY5Y cells (45), but not in MAO-B-containing Caco-2 and U118MG cells (46,47). These studies are consistent with present findings regarding the significant upregulation of Bcl-2 and improved survival of NSCs in response to 20 µM selegiline.…”

Section: Discussionmentioning

confidence: 71%

Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

et al. 2017

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Abstract. Oxidative stress and reactive oxygen species generation have been implicated in the pathogenesis of several neurological disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. In the present study, the neuroprotective effects of selegiline against hydrogen peroxide-induced oxidative stress in hippocampus-derived neural stem cells (NSCs) were evaluated. NSCs isolated from neonatal Wistar rats were pretreated with different doses of selegiline for 48 h and then exposed to 125 µM H 2 O 2 for 30 min. Using MTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, acridine orange/ethidium bromide staining and reverse transcription-quantitative polymerase chain reaction, the effects of selegiline on cell survival, apoptosis and the expression of B-cell lymphoma 2 (Bcl-2) and heat shock protein 4 (Hspa4) in pretreated stem cells were assessed compared with a control group lacking pretreatment. The results indicated that the viability of cells pretreated with 20 µM selegiline was significantly increased compared with the control group (P<0.05). Additionally, 20 µM selegiline increased the mRNA expression of Bcl-2 and Hspa4 (P<0.05 vs. control) and suppressed oxidative stress-induced cell death (apoptosis and necrosis; P<0.05 vs. control and 10 µM groups). From these findings, it was concluded that selegiline may be a therapeutic candidate for the treatment of neurological diseases mediated by oxidative stress. IntroductionThe most common neorodegenerative disorders, namely Alzheimer's disease (AD) and Parkinson's disease (PD), are prevalent in ~1% of individuals aged 60 years and older (1). Their etiologies remain uncertain, though there are a number of established pathogenic factors, including oxidative stress, neural apoptosis, mitochondrial dysfunction, excitotoxicity, impairment of the ubiquitin-proteasome system and inflammation (2,3). Neuroprotective therapy has been suggested to prevent disease progression by inhibiting the action of pathogenic factors, for instance, by reducing the production of reactive oxygen species (ROS) (4). Overproduction of ROS may cause oxidative damage to biomolecules and subsequently DNA damage, ultimately leading to the development of neurodegenerative diseases. According to studies on PD, inhibitors of type B monoamine oxidase (MAO), including selegiline [also known as (-)-deprenyl] and rasagiline, are among the most promising neuroprotective agents identified to date (5-7). MAO exists in two forms, MAO-A and -B. The catalytic activity of these enzymes generates H 2 O 2 and nitrogen species, which are toxic products that may cause oxidative damage to mitochondrial DNA (mtDNA) and thus have potential implications for apoptosis, aging and neurodegenerative processes (8). The MAO-B inhibitor, selegiline, is typically recommended as a first-line treatment for PD and has been demonstrated to possess neuroprotective functions (9); notably, this inhibitor protected neuronal cells against induc...

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“…Normally the H 2 O 2 is then inactivated by glutathione peroxidase but it can be converted, chemically, by Fe 2+ ions (Fenton reaction) into the highly reactive hydroxyl radical. This radical has widespread deleterious effects which can cause neuronal damage and death and may account for associated health-related problems [51,54].…”

Section: Monoamine Oxidasementioning

confidence: 99%

Mitochondrial Functions in Mood Disorders

Hroudová¹,

Fišar²,

Raboch³

2013

Mood Disorders

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Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading to cell death or neuroprotection

Cited by 74 publications

References 47 publications

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

Mitochondrial Functions in Mood Disorders

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