Mitophagy Regulates Neurodegenerative Diseases

Cen, Xufeng; Zhang, Manke; Zhou, Mengxin; Ye, Lingzhi; Xia, Hong

doi:10.3390/cells10081876

Cited by 27 publications

(19 citation statements)

References 151 publications

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“…When damaged, mitochondria produce escalating amounts of ROS, ultimately leading to ATP deficiency and bioenergetics collapse [3,15,32,33]. Many aspects of mitochondrial dysfunction have been observed in neurodegenerative conditions: change in their size and number, abnormal mitochondrial dynamics, reduced energy metabolism, reduced expression and activity of key enzymes of oxidative metabolism, increased rate of mutations in mitochondrial DNA (mtDNA), increased vulnerability to ROS attack and activation of intrinsic apoptotic pathway components (although not necessarily leading to apoptosis) [7,21,34,35]. OS-induced endoplasmic reticulum (ER) stress, calcium overload and disturbance of mitochondrial calcium homeostasis further contribute to mitochondrial failure and disease progression [7,[36][37][38].…”

Section: Oxidative Stress In Neurodegenerative Diseases: the Role Of Nrf2 Pathwaymentioning

confidence: 99%

“…Together with the unique fingerprint that is typical for each of these diseases (mostly related to distinct proteins that form deposits and the selective vulnerability of specific brain areas), they all have several underlying mechanisms in common. These include oxidative stress (OS), impairment of mitochondrial function, excitotoxicity, chronic inflammatory response and gliosis, protein misfolding, aggregation and accumulation, deregulation of autophagy and proteosomal protein degradation, alterations in the brain lipid profile and disturbed ceramide metabolism, impairment of synaptic function and, ultimately, neuronal death [2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

et al. 2021

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Neurodegenerative diseases are one of the leading causes of disability and death worldwide. Intracellular transduction pathways that end in the activation of specific transcription factors are highly implicated in the onset and progression of pathological changes related to neurodegeneration, of which those related to oxidative stress (OS) and neuroinflammation are particularly important. Here, we provide a brief overview of the key concepts related to OS- and neuroinflammation-mediated neuropathological changes in neurodegeneration, together with the role of transcription factors nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB). This review is focused on the transcription factor p53 that coordinates the cellular response to diverse genotoxic stimuli, determining neuronal death or survival. As current pharmacological options in the treatment of neurodegenerative disease are only symptomatic, many research efforts are aimed at uncovering efficient disease-modifying agents. Natural polyphenolic compounds demonstrate powerful anti-oxidative, anti-inflammatory and anti-apoptotic effects, partially acting as modulators of signaling pathways. Herein, we review the current understanding of the therapeutic potential and limitations of flavonols in neuroprotection, with emphasis on their anti-oxidative, anti-inflammatory and anti-apoptotic effects along the Nrf2, NF-κB and p53 pathways. A better understanding of cellular and molecular mechanisms of their action may pave the way toward new treatments.

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Section: Oxidative Stress In Neurodegenerative Diseases: the Role Of Nrf2 Pathwaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

et al. 2021

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“…Mitochondria plays an important role in the pathogenesis of PD ( González-Rodríguez et al, 2021 ) ( Sanchez-mirasierra et al, 2021 ) ( Cen et al, 2021 ). Mitophagy is the selective autophagy mechanism that targets mitochondria to the autophagy pathway ( Lemasters, 2005 ) via specific mitophagy receptors such as optineurin (OPTN) or nuclear dot protein 52 kDa (NDP52) ( Lazarou et al, 2015 ), ( Heo et al, 2015 ).…”

Section: Mitophagymentioning

confidence: 99%

Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease

Sanchez-Mirasierra

Ghimire

Hernández-Díaz

et al. 2022

Front. Cell Dev. Biol.

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Macroautophagy, an evolutionary conserved catabolic process in the eukaryotic cell, regulates cellular homeostasis and plays a decisive role in self-engulfing proteins, protein aggregates, dysfunctional or damaged organelles, and invading pathogens. Growing evidence from in vivo and in vitro models shows that autophagy dysfunction plays decisive role in the pathogenesis of various neurodegenerative diseases, including Parkinson’s disease (PD). PD is an incurable and second most common neurodegenerative disease characterised by neurological and motor dysfunction accompanied of non-motor symptoms that can also reduce the life quality of patients. Despite the investment in research, the aetiology of the disease is still unknown and the therapies available are aimed mostly at ameliorating motor symptoms. Hence, therapeutics regulating the autophagy pathway might play an important role controlling the disease progression, reducing neuronal loss and even ameliorating non-motor symptoms. In this review, we highlight potential therapeutic opportunities involved in different targeting options like an initiation of autophagy, Leucine-rich repeat kinase 2 (LRRK2) inhibition, mitophagy, lysosomes, lipid metabolism, immune system, gene expression, biomarkers, and also non-pharmacological interventions. Thus, strategies to identify therapeutics targeting the pathways modulating autophagy might hold a future for therapy development against PD.

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“…The importance of mitophagy in the pathogenesis of neurodegenerative diseases is supported by the identified mutations of proteins involved in mitophagy—primarily PINK1 and parkin in Parkinson’s disease, optineurin and TBK1 in amyotrophic lateral sclerosis [ 17 , 18 , 19 ], and p62/SQSTM1 in frontotemporal dementia [ 20 ]. In addition to genetic disorders of the mitophagy pathway in a number of neurodegenerative diseases, including Alzheimer’s disease, the role of accumulation of damaged mitochondria in neurons is emphasized, as well as mitophagy disorders resulting from the interaction of components of the mitophagy pathway, for example, Drp1, with the accumulation pathological proteins, such as synuclein, tau protein, and beta-amyloid, in neurons [ 21 , 22 , 23 ].…”

Section: Mitophagy In Neurons In Aging and Neurodegenerationmentioning

confidence: 99%

Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

Сухоруков

Воронков

Баранич

et al. 2021

IJMS

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Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

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Mitophagy Regulates Neurodegenerative Diseases

Cited by 27 publications

References 151 publications

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease

Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

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